Ch. 3 The Cell Nucleus (E2) Flashcards
A membrane-limited compartment that contains the genome (genetic information) in eukaryotic cells, together with the machinery for DNA replication and RNA transcription and processing.
What is the nucleus?
A non-dividing cell is also called an {…} cell.
Interphase
The nucleus of an interphase cell consists of 4 major components. List them.
1) Chromatin
2) Nucleolus
3) Nuclear envelope
4) Nucleoplasm
This nuclear material contains DNA associated with roughly an equal mass of various nuclear proteins (e.g., histones) that are necessary for DNA to function.
What is chromatin?
In what 2 ways is chromatin organized?
Euchromatin & heterochromatin
A SMALL AREA within the nucleus that contains DNA in the form of transcriptionally active ribosomal RNA (rRNA) genes, RNA, and proteins, making it the SITE OF rRNA SYNTHESIS and INITIAL RIBOSOMAL ASSEMBLY. This area/structure also contains REGULATORY CELL CYCLE PROTEINS.
What is the nucleolus?
A double membrane system that surrounds the nucleus of the cell. It consists of an inner and an outer membrane separated by a perinuclear cisternal space and perforated by NUCLEAR PORES.
What is the nuclear envelope?
The outer membrane of the nuclear envelope is continuous with that of the {…} and is often studded with ribosomes.
rER (rough endoplasmic reticulum)
Nuclear content other than the chromatin and nucleolus.
What is the nucleoplasm?
Evaluation of nuclear size, shape, and structure plays an important role in this disease.
What is cancer?
The disappearance of nuclei due to complete dissolution of DNA by increased activity of DNAse as seen in DYING CELLS.
What is karyolysis?
Condensation of chromatin leading to shrinkage of the nuclei (they appear as dense basophilic masses) as seen in DYING CELLS.
What is pyknosis?
Fragmentations of nuclei (these changes are usually preceded by pyknosis) as seen in DYING CELLS.
What is karyorrhexis?
Chromatin, a complex of DNA and proteins, is responsible for the characteristic {…} (i.e., affinity/love for alkaline/basic pH) of the nucleus.
Basophilia
Why is DNA organized as chromatin?
The length of a DNA molecule is MUCH longer than the nuclear diameter, so it must be tightly folded and organized
Further folding of chromatin, such as that which occurs during mitosis, produces these structures.
What are chromosomes?
Chromatin proteins include five basic proteins called {…} along with other {…} proteins.
1) Histones
2) Non-histone
The human {…} encompasses the entire length of human DNA that contains the genetic information packaged in all 46 chromosomes.
Genome
In what year was the sequencing for the human genome completed?
2003
Recent discoveries have revealed that large segments of DNA can vary in numbers of copies. For instance, genes that were thought to always occur in two copies per genome have sometimes one, three, or more copies. Such {…} are widespread in the human genome and most likely lead to genetic imbalances.
CNVs (copy number variations)
A union of genomic sequences encoding a coherent set of potentially overlapping functional products (i.e., polypeptides).
What is a gene?
In general, two forms of chromatin are found in the nucleus: a condensed form called {…} and a dispersed form called {…}.
1) Heterochromatin
2) Euchromatin
Which form of chromatin is densely stained during slide preparation? Heterochromatin or euchromatin?
Heterochromatin
Which form of chromatin is lightly stained during slide preparation? Heterochromatin or euchromatin?
Euchromatin
Which form of chromatin is transcriptionally active (i.e., genes are actively being copied from DNA into mRNA)?
NOTE: Think about the chromatin structure. In which form can chromatin be easily read and transcribed?
Euchromatin
This type of heterochromatin contains the same regions of genetically inactive, highly repetitive sequences of DNA that are condensed and consistently packaged in the same regions of the chromosome when compared with other cells. It is found in large amounts near CENTROMERES and TELOMERES.
What is constitutive heterochromatin?
This type of heterochromatin is not repetitive, and its location within the nucleus and chromosomes varies when compared with other cells.
What is facultative heterochromatin?
Facultative heterochromatin may undergo active transcription in certain cells, such as this inactive X chromosome found in female mammals.
What is a Barr body?
List 3 locations in which you will find heterochromatin.
1) Marginal chromatin
2) Karyosomes
3) Nucleolar-associated chromatin
The structure that light microscopists formerly referred to as the nuclear membrane actually consists largely of {…} chromatin, which is found at the PERIPHERY OF THE NUCLEUS.
Marginal
Discrete bodies of chromatin irregular in size and shape that are found throughout the nucleus.
What are karyosomes?
Chromatin found in association with the nucleolus.
What is nucleolar-associated chromatin?
Euchromatin is prominent in metabolically {…} cells, such as neurons and liver cells. Heterochromatin predominates in metabolically {…} cells, such as small circulating lymphocytes and sperm cells, or in cells that produce one major product, such as plasma cells.
1) Active
2) Inactive
The smallest units (10-nm diameter) of chromatin structure are macromolecular complexes of DNA and histones called these.
What are nucleosomes?
Describe the 1st step of chromatin folding.
DNA coils around a protein core, forming the nucleosome, and shortening the DNA molecule approximately seven-fold
The core of the nucleosome consists of eight histone molecules called an…
Octamer
When chromatin is extracted from the nucleus, the nucleosomal substructure of chromatin is visible in transmission electron microscopy (TEM) and is often described as this phrase.
What are “beads on a string?”
Describe the 2nd level of chromatin folding.
A long strand of nucleosomes coils to produce a 30-nm chromatin fibril
How many nucleosomes comprise 1 turn in the coil of the chromatin fibril?
6
Long stretches of 30-nm chromatin fibrils are further organized into {…} domains (containing 15,000–100,000 base pairs), which are anchored into a CHROMOSOME SCAFFOLD or NUCLEAR MATRIX composed of non-histone proteins.
Loop
In dividing cells, chromatin is condensed and organized into discrete bodies called these.
What are chromosomes?
Each chromosome is formed by two {…} that are joined together at a point called the {…}
1) Chromatids
2) Centromere
The area located at each end of the chromosome.
What is the telomere?
To survive indefinitely (become “immortalized”), cells must activate a mechanism that maintains telomere length. For example, in cells that have been transformed into malignant cells, an enzyme called {…} is present that adds repeated nucleotide sequences to the telomere ends.
Telomerase
Telomerase is being studied as a potential target for use as an {…} treatment.
Anticancer
With the exception of the mature gametes, the egg and sperm, human cells contain {…} chromosomes organized as 23 {…} pairs (each chromosome in the pair has the same shape and size).
1) 46
2) Homologous
The 1st 22 pairs of homologous chromosomes are referred to as these.
What are autosomes?
The 23rd pair of chromosomes are referred to as these.
What are sex chromosomes?
The chromosomal number, 46, is found in most of the somatic cells of the body and is called the {…} (2n) number.
Diploid
To simplify the description of chromosomal number and DNA changes during mitosis and meiosis, we use the lowercase letter {…} for chromosome number and lowercase letter {…} for DNA content.
1) (n)
2) (d)
As a result of meiosis, eggs and sperm have only 23 chromosomes, the {…} (1n) number, as well as the {…} (1d) amount of DNA.
1) Haploid
2) Haploid
The somatic chromosome number (2n) and the diploid (2d) amount of DNA are restored at {…} by the fusion of the sperm nucleus with the egg nucleus.
Fertilization
A preparation of chromosomes derived from mechanically ruptured, dividing cells that are then fixed, plated on a microscope slide, and stained.
What is a metaphase spread?
In what 3 ways are chromosome pairs sorted in a karyotype?
1) Size
2) Shape
3) Emitted fluorescent color
What is the name of the current/modern procedure used to visualize a chromosomal spread?
Fluorescent in-situ hybridization (FISH)
Image-processing software is used to sort the chromosome pairs according to their morphology to form this.
What is a karyotype?
A variety of molecular probes that are now commercially available are used in {…} testing to diagnose disorders caused by chromosomal abnormalities, such as nondisjunctions, transpositions, deletions, and duplications of specific gene sites.
Cytogenetic
One X chromosome was discovered in 1949 by Barr and Bartram in nerve cells of female cats, where it appears as a well-stained round body, now called this structure, adjacent to the nucleolus.
What is the Barr body?
In females, the Barr body represents a region of {…} heterochromatin that is condensed and not involved in the transcription process.
Facultative
The Barr body can be used to identify the {…} of a fetus.
Sex
When is the Barr body formed, how is it decided which X chromosome becomes the Barr body, and how long does the Barr body stay maintained?
The Barr body is formed during embryonic development and is randomly chosen. It stays condensed for the rest of the organism’s lifetime
These regions on the nucleolus contain DNA loops of five different chromosomes (13, 14, 15, 21, and 22) that contain rRNA genes, RNA polymerase I, and transcription factors.
What are fibrillar centers?
This region of the nucleolus contains ribosomal genes that are actively undergoing transcription and large amounts of rRNA.
What is the fibrillar material (pars fibrosa)?
This region of the nucleolus represents the site of initial ribosomal assembly and contains densely packed preribosomal particles.
What is the granular material (pars granulosa)?
The network formed by the granular and the fibrillar materials.
What is the nucleolonema?
A p53-binding protein found within the nucleolus that regulates the cell cycle and influences cell differentiation. As cellular differentiation progresses, the level of this protein decreases.
What is nucleostemin?
Describe the relationship between the protein nucleostemin and cell differentiation.
As differentiation progresses, nucleostemin levels decrease
The presence of {…} in MALIGNANT CELLS suggests that it could play a role in their UNCONTROLLED PROLIFERATION.
Nucleostemin
In addition, DNA, RNA, and retroviruses and their viral proteins interact with the nucleolus and cause redistribution of {…} and {…} materials during the course of VIRAL INFECTION. These viruses may use components of the {…} as part of their own REPLICATION PROCESS.
1) Fibrillar
2) Granular
3) Nucleolus
Evidence suggests that viruses may target the {…} and its components to favor viral {…} and {…} and perhaps alter the cell cycle to promote viral {…}.
1) Nucleolus
2) Transcription
3) Translation
4) Replication
An important component in the diagnosis and evaluation of genetic disorders and refers to the analysis of chromosomes.
What is cytogenetic testing?
Sometimes, part of a chromosome will break off and attach to another chromosome. When this happens, it is referred to as this.
What is a translocation?
Severe intellectual disability, muscular hypotonia, short stature, hypogonadism, and insulin-resistant diabetes are characteristics of this genetic disease caused by the deletion of the D15S10 gene.
What is Prader-Willi/Angelman syndrome (PWS/AS)?
Inheriting a D15S10 deletion from the mother results in {…}, but inheriting the deletion from the father results in {…}.
1) AS
2) PWS
Mutations in these 2 genes are associated with an increased risk for bilateral breast cancer and ovarian cancer.
What are breast cancer susceptibility genes 1 & 2 (BRCA-1 & BRCA-2)?
What are the two functions of the RAD-51 protein?
1) DNA repair
2) Homologous recombination
What is the purpose of the p53 gene?
To encode proteins for apoptosis-based tumor suppression
The nucleolus stains intensely with {…} and {…} dyes and metachromatically with {…} dyes.
1) Hematoxylin
2) Basic
3) Thionine
The selectively permeable membranous barrier between the nuclear compartment & the cytoplasm. It also encloses the chromatin.
What is the nuclear envelope?
The space between the outer and inner nuclear membranes.
What is the perinuclear cisternal space?
The perinuclear clear cisternal space is continuous with the cisternal space of this organelle.
What is the rough ER?
These openings perforate the inner and outer nuclear membranes to mediate the active transport of proteins, ribonucleoprotein, and RNAs between the nucleus and the cytoplasm.
What are nuclear pores?
Which portion of the nuclear membrane closely resembles the membrane of the ER and is continuous with the rER membrane?
The outer membrane
Polyribosomes are often attached to ribosomal {…} proteins present on the {…} side of the outer nuclear membrane.
1) Docking
2) Cytoplasmic
The {…} nuclear membrane is supported by a rigid network of intermediate protein filaments attached to its inner surface called the nuclear (fibrous) {…}.
1) Inner
2) Lamina
The thin, electron-dense intermediate filament network-like layer that resides underneath the nuclear membrane, which is essential in many nuclear activities, such as DNA replication, transcription, and gene regulation.
What is the nuclear lamina?
The major components of the lamina, as determined by biochemical isolation, are nuclear {…}, a specialized type of nuclear intermediate filament, and {…} proteins.
1) Lamins
2) Lamin-associated
How do lamin proteins A, B, and C interact with each other?
Lamins A & C comprise intermediate filaments that are cross-linked into an orthogonal lattice and attach to the inner nuclear membrane via the lamin B protein
The family of lamin receptors includes {…} (34 kDa) that binds both lamin A and B; {…} (29 kDa) that binds lamin A; and a 58-kDa {…} (LBR) that, as its name suggests, binds lamin B.
1) Emerin
2) Nurim
3) Lamin B receptor
Unlike other cytoplasmic intermediate filaments, lamins {…} during mitosis and {…} when mitosis ends. The nuclear lamina appears to serve as {…} for chromatin, chromatin-associated proteins, nuclear pores, and the membranes of the nuclear envelope.
1) Disassemble
2) Reassemble
3) Scaffolding
Impairment in nuclear lamina architecture or function is associated with certain genetic diseases (i.e., {…}) and {…}. Mutations in lamin {…} cause tissue-specific diseases that affect striated muscle, adipose tissue, peripheral nerve or skeletal development, and premature aging.
1) Laminopathies
2) Apoptosis
3) A/C
This disorder is characterized by early-onset contractures of major tendons, slowly progressive muscle weakness, muscle wasting in the upper and lower limbs, and cardiomyopathy (i.e., weakening of the heart muscle).
What is Emery-Dreifuss muscular dystrophy (EDMD)?
Two hereditary forms of Emery–Dreifuss muscular dystrophy (EDMD) are associated with mutations in either {…} or lamin {…}.
1) Lamins
2) Receptors
The {…} recessive form of EDMD is caused by mutations of {…}, whereas the {…} dominant form of EDMD is caused by mutations in lamin {…}.
1) X-linked
2) Emerin
3) Autosomal
4) A/C
These 70- to 80-nm openings along the nuclear envelope are formed from the merging of the inner and outer membranes of the nuclear envelope.
What are nuclear pores?
This term is used to describe a small, dense body observed with a transmission electron microscope (TEM); they can be found in the center of a nuclear pore’s opening. Such profiles are thought to represent either ribosomes or other protein complexes (transporters) captured during their passage through the pore at the time of fixation.
What are central plugs/transporters?
With special techniques, the nuclear pore exhibits additional structural detail. Eight multidomain protein subunits arranged in an octagonal CENTRAL FRAMEWORK at the periphery of each pore form a CYLINDER-LIKE STRUCTURE known as the {…} (NPC).
Nuclear pore complex
The NPC is composed of approximately 50 different NPC proteins collectively referred to as…
Nucleoporins (Nup proteins)
What 2 structures is the central framework of the nuclear pore complex (NPC) situated between?
Cytoplasmic & nuclear rings
From the cytoplasmic ring, eight of these short structures protrude into the cytoplasm and point toward the center of the structure.
What are protein fibrils?
The nucleoplasmic ring complex anchors a NUCLEAR {…} (or nuclear “cage” that resembles a fish trap) assembled from eight thin 50-nm-long filaments joined distally by an adjustable {…} RING 30–50 nm in diameter
1) Basket
2) Terminal
The cylinder-shaped central framework encircles the {…} PORE of the NPC, which acts as a close-fitting diaphragm or gated channel. In addition, each NPC contains one or more {…} channels for the transport of {…} molecules.
1) Central
2) Water-filled
3) Small
The nuclear pore complex (NPC) mediates this type of transport.
What is bidirectional nucleocytoplasmic transport?
What factor does transport through the nuclear pore complex (NPC) depend on?
Size of the molecule
Large molecules (such as large proteins and macromolecular complexes) depend on the presence of an attached signal sequence called the {…} (NLS) for passage through the pores.
Nuclear localization signal
Proteins labeled with NLS destined for the nucleus then bind to a soluble cytosolic receptor called a {…} (i.e., importin) that directs them from the cytoplasm to an appropriate NPC.
Nuclear import receptor
This mechanism actively transports large molecules destined for the nucleus through a nuclear pore.
What is a GTP energy-dependent mechanism?
Export of proteins and RNA from the nucleus is similar to the import mechanism into the nucleus. Proteins that possess a […} (NES) bind in the nucleus to {…} (a protein that moves molecules from the nucleus into the cytoplasm) and to a GTP molecule.
1) Nuclear export sequence
2) Exportin
Ions and smaller water-soluble molecules (<9 Da) may cross the {…} channels of the NPC by {…} diffusion. This process is {…} and does NOT require nuclear signal proteins.
1) Water-filled
2) Simple
3) Nonspecific
This somatic cell population class consists of cells that no longer divide (postmitotic cells), such as cells of the central nervous system and skeletal or cardiac muscle cells. Under certain circumstances, some of these cells (i.e., cardiac myocytes) may enter mitotic division.
What are static cell populations?
This somatic cell population consists of cells that divide episodically and slowly to maintain normal tissue or organ structure. These cells may be stimulated by injury to become more mitotically active. Periosteal and perichondrial cells, smooth muscle cells, endothelial cells of blood vessels, and fibroblasts of the connective tissue may be included in this category.
What are stable cell populations?
This somatic cell population class may be slowly or rapidly renewing but display regular mitotic activity. Division of such cells usually results in two daughter cells that differentiate both morphologically and functionally or two cells that remain as stem cells. Daughter cells may divide 1 or more times before their mature state is reached. The differentiated cell may ultimately be lost from the body.
What are renewing cell populations?
This somatic cell population class includes include smooth muscle cells of most hollow organs, fibroblasts of the uterine wall, and epithelial cells of the lens of the eye and may actually slowly increase in size during life, as do the smooth muscle cells of the gastrointestinal tract and the epithelial cells of the lens.
What are slowing renewing populations?
This somatic cell population class includes blood cells, epithelial cells and dermal fibroblasts of the skin, and the epithelial cells and subepithelial fibroblasts of the mucosal lining of the alimentary tract.
What are rapidly renewing populations?
What is the goal of the cell cycle in RENEWING and GROWING cell populations?
To produce two daughter cells, each containing chromosomes identical to those of the parent
What are the 2 principle phases of the cell cycle?
Interphase & M phase (mitosis)
This phase of the cell cycle represents continuous growth of the cell.
What is interphase?
This phase of the cell cycle is characterized by the partition of the genome.
What is M phase?
What are the 3 other phases of the cell cycle that subdivide interphase?
G1 (gap 1), S (synthesis), & G2 (gap 2) phases
How long does it take rapidly renewing populations of human cells to progress through a full cell cycle?
24 hours
Throughout the cycle, several internal quality control mechanisms or {…} represented by biochemical pathways control the transition between cell cycle stages.
Checkpoints
What is the purpose of cell cycle checkpoints?
To ensure that certain conditions are met before proceeding to the next step/checkpoint
The longest and most variable phase of the cell cycle.
What is G1?
List the phases of the cell cycle in order.
1) G1
2) S
3) G2
4) M
During this portion of interphase, the cell gathers nutrients and synthesizes RNA and proteins necessary for DNA synthesis and chromosome replication.
What is G1?
This G1 checkpoint is sensitive to the size of the cell, the state of the cell’s physiologic processes, and its interactions with extracellular matrix.
What is the restriction checkpoint?
This G1 checkpoint monitors the integrity of newly replicated DNA.
What is the G1 DNA damage checkpoint?
What happens if the G1 DNA damage checkpoint detects high levels of TUMOR SUPPRESSOR PROTEIN p53?
The checkpoint will not allow the cell to enter the S phase, and it will likely undergo apoptosis
What is the most important checkpoint in the cell cycle? Why?
NOTE: For the “why,” the cell is facing an ultimatum that will decide its fate
The restriction checkpoint is the most important b/c it’s at this point that the cell evaluates its replicative potential before either entering S phase or retiring to leave the cell cycle
A cell that leaves the cycle in the G1 phase usually begins {…} (GTD) by entering the {…} phase (“O” stands for “outside” the cycle).
1) Terminal differentiation
2) GO
The restriction (i.e., “point of no return”) checkpoint is mediated by interactions between the {…} (pRb) and a family of {…} (E2F) with target promoters
1) Retinoblastoma susceptibility protein
2) Essential transcription factors
What does a proper interaction between pRb and E2F do in normal cells?
NOTE: 2 functions of this interaction
Turns off many genes and blocks cell cycle progression
In this portion of interphase, DNA is replicated (i.e., DNA content is doubled and new chromatids form).
What is S phase?
Chromosome replication in the S phase is initiated at many different sites called {…} along the chromosomal DNA.
Replicons
This S phase checkpoint monitors the quality of replicating DNA.
What is the S DNA damage checkpoint?
This phase of the cell cycle prepares the cell for cell division.
What is G2?
What 2 things does G2 do to prepare the cell for division?
1) Cell growth
2) Reorganization of cytoplasmic organelles
How long does the G2 phase last? There are 2 answers.
1) 1 hr in rapidly dividing cells
2) Nearly indefinitely in some polyploid cells and in cells arrested in G2 for long periods (e.g., primary oocytes)
What are the 2 checkpoints that monitor the DNA quality in G2? Which one prevents the progression of the cell into the M phase before DNA synthesis is complete?
1) G2 DNA damage checkpoint
2) Unreplicated DNA checkpoint
Unreplicated DNA checkpoint prevents progression to the M phase
How long does the M phase (mitosis) last?
About an hour
Mitosis nearly always includes both {…} (i.e., division of the nucleus) and {…} (i.e., division of the cell).
1) Karyokinesis
2) Cytokinesis
What event concludes the M phase?
Separation of 2 identical daughter cells
This M phase checkpoint prevents the premature entry into anaphase.
What is the spindle-assembly checkpoint?
This M phase checkpoint prevents the process of cytokinesis until all of the chromosomes have been correctly separated.
What is the chromosome-segregation checkpoint?
Malfunction of any of the three DNA-damage checkpoints at the G1, S, and G2 phases of the cell cycle and the spindle-assembly checkpoint at the M phase may lead to this event.
What is a mitotic catastrophe?
Define mitotic catastrophe.
The failure to arrest the cell cycle before or at mitosis, resulting in aberrant (i.e., abnormal) chromosome segregation
Cells that fail to execute the apoptotic cycle in response to DNA or mitotic spindle damage are likely to divide asymmetrically in the next round of cell division. This leads to the generation of {…} cells (cells containing abnormal chromosome numbers). Thus, a mitotic catastrophe may be regarded as one of the mechanisms contributing to {…} (tumor cell development).
1) Aneuploid
2) Oncogenesis
The malfunction of the G1 restriction checkpoint may be facilitated by viral proteins of several cancer-causing viruses, such as the {…} (SV40) that binds to {…} (pRb).
1) T antigen of simian virus
2) Retinoblastoma susceptibility protein
How does the binding of the T antigen of simian virus (SV40) and pRb protein (i.e., the pRb-T antigen complex) lead to cancer?
NOTE: Think about how this affects the G1 restriction checkpoint
The antigen complex deactivates the G1 restriction checkpoint, facilitating the progression from G1 to S phase without checking considering if the cell is healthy enough to be replicated
Malfunction of the G1 restriction checkpoint results in cancers, such as {…} (cancer of the lining epithelium of the pleural cavities in the thorax), {…} (a type of bone cancer), and {…} (a type of childhood brain tumor).
1) Mesothelioma
2) Osteosarcoma
3) Ependymoma
G0 cells that can be induced to re-enter the cell cycle in response to injury.
NOTE: G0/GO cells are the retired cells that exit the cell cycle following their judgment at the G1 restriction checkpoint
What are reserve stem cells?
The 2-protein complex that helps the cells power through the checkpoints of the cell cycle.
What is the cyclin-Cdk complex?
NOTE: Cdk = cyclin-dependent kinase
This protein, discovered in the early 1970s, was believed to have controlled the initiation of mitosis.
What is the maturation-promoting factor (MPF)?
What 2 proteins comprised the maturation-promoting factor (MPF)?
Cdc2 (Cdk-1) & cyclin B
What 3 features does the cell division process provide?
1) Increased cell number
2) Renewed cell populations
3) Wound repair
The equal partitioning of replicated chromosomes and their genes into two identical groups.
What is mitosis?
At the beginning of the S phase, the chromosome number is (2n), and the DNA content is also (2d); at the end, the chromosome number remains the same (2n), but the DNA content doubles to…
4d
In this mitotic phase, the replicated chromosomes condense and become visible. As the chromosomes continue to condense, each of the four chromosomes derived from each homologous pair consists of two chromatids.
What is prophase?
In prophase, the sister chromatids are held together by a ring of proteins called {…} and the {…}.
1) Cohesins
2) Centromere
In late prophase or {…} (sometimes identified as a separate phase of mitosis), the nuclear envelope begins to disintegrate into small transport vesicles and resembles the smooth ER (sER).
Prometaphase
The {…}, which may still be present in some cells, also completely disappears in prometaphase. In addition, a highly specialized protein complex called a {…} appears on each chromatid opposite to the centromere.
1) Nucleolus
2) Kinetochore
The protein complexes that form kinetochores in the centromere region of the chromatids are attached to specific repetitive DNA sequences known as these, which are similar in each chromosome.
What is satellite DNA?
In this mitotic phase, the mitotic spindle becomes organized around the microtubule-organizing centers (MTOCs) located at opposite poles of the cell.
What is metaphase?
These mitotic spindles are nucleated from γ-tubulin rings in a star-like manner around each MTOC & are responsible for positioning the spindle within the cell.
What are astral microtubules?
These mitotic spindles, also originating from the MTOC, constitute all microtubules lying between spindle poles that are not connected to kinetochores.
What are polar microtubules?
These mitotic spindles emanate from the MTOC to probe the cytoplasm in search of kinetochores.
What are kinetochore microtubules?
Kinetochore microtubules and their associated motor proteins direct the movement of the chromosomes to a plane in the middle of the cell referred to as this plate.
What is the equatorial/metaphase plate?
This mitotic phase begins at the initial separation of sister chromatids. This separation occurs when the cohesins that have been holding the chromatids together break down. The chromatids then begin to separate and are pulled to opposite poles of the cell by the molecular motors (dyneins) sliding along the kinetochore microtubules toward the MTOC.
What is anaphase?
This mitotic phase is marked by the reconstitution of the nuclear envelope around the chromosomes at each pole. The chromosomes uncoil and become indistinct, except at regions that will remain condensed in the interphase nucleus. The nucleoli reappear, and the cytoplasm divides (cytokinesis) to form two daughter cells.
What is telophase?
How does cytokinesis begin?
The plasma membrane midway between the poles of the mitotic spindle begins to furrow
Separation at the {…} furrow is achieved by a {…} ring consisting of a very thin array of {…} filaments positioned around the perimeter of the cell. Within the ring, {…} molecules are assembled into small filaments that interact with the actin filaments, causing the ring to contract.
1) Cleavage
2) Contractile
3) Actin
4) Myosin II
Following telophase, the DNA content and chromosome number are both…
Diploid (2d & 2n, respectively)
This cellular process involves two sequential nuclear divisions followed by cell divisions that produce gametes containing half the number of chromosomes and half the DNA found in somatic cells.
What is meiosis?
The {…} (the cell resulting from the fusion of an ovum and a sperm) and all the somatic cells derived from it are {…} chromosome number; thus, their cells have two copies of every chromosome and every gene encoded on this chromosome. These chromosomes are called {…} chromosomes because they are similar, but not identical.
1) Zygote
2) Diploid
3) Homologous
Why are a zygote’s homologous chromosomes considered similar but NOT identical?
B/c one set of chromosomes is inherited from the mother, and one is inherited from the father
The gametes, having only one member of each chromosome pair, are described as {…} (1n).
Haploid
During gametogenesis, the number of chromosomes is reduced to the {…} state (23 chromosomes in humans) through {…}, a process that involves two successive divisions, the second of which is not preceded by an {…} phase.
1) Haploid
2) Meiosis
3) S
Why is the chromosome reduction in meiosis necessary for species survival?
To maintain a constant number of chromosomes in a given species
When are chromosome number and DNA content reduced to haploid states in meiosis?
Chromosome number - 1st meiotic division
DNA content - 2nd meiotic division
During meiosis, the chromosome pair may exchange chromosome segments, thus altering the genetic composition of the chromosomes. This genetic exchange is called…
Crossing over
What is the purpose of crossing over in haploid gametes?
To promote genetic diversity
How do meiotic products differ in the male (i.e., primary spermatocyte) and female (i.e., primary oocyte)?
Male - 4 structurally identical, genetically unique haploid spermatids that can each differentiate into a spermatozoon
Female - 1 haploid ovum, 3 haploid polar bodies
Of the 4 female meiotic products, which one receives the most cytoplasm and becomes a functional gamete?
The ovum
Meiosis consists of two successive mitotic divisions without the additional {…} phase between the two divisions.
S
Why is meiosis I called reductional division?
Chromosome number goes from diploid to haploid, and DNA content goes from (4d) to (2d)
Why is meiosis II called equatorial division?
Chromosome number doesn’t change from meiosis I, but the DNA content is reduced to (1d)
In meiosis II, the amount of DNA is presented by the number of these nuclear structures.
What are chromatids?
When does crossing over (i.e., genetic recombination occur)? Meiosis I or II?
Meiosis I
What 3 things happen to homologous chromosomes during the prophase of meiosis I?
1) Pairing
2) Synapsis (i.e., close association of homologous chromosomes)
3) Recombination
This stage of prophase I is characterized by the condensation of chromatin and appearance of chromosomes.
STEP 1
What is leptotene?
The sister chromatids during the leptotene stage of prophase I also condense and become connected with each other via these complexes.
What are meiosis-specific cohesion complexes (Rec8p)?
Synapsis, the close association of homologous chromosomes, begins at this stage in prophase I and continues throughout pachytene.
STEP 2
What is zygotene?
The synapsis process of the zygotene stage involves the formation of a {…} complex, a tripartite structure that binds the chromosomes together.
Synaptonemal
At this stage in prophase I, synapsis is complete. Crossing-over occurs early in this phase and involves the transposition of DNA strands between two different chromosomes.
STEP 3
What is pachytene?
Early in this stage of prophase I, the synaptonemal complex dissolves, and the chromosomes condense further.
STEP 4
What is diplotene?
Homologous chromosomes in the diplotene stage of prophase I begin to separate from each other and appear to be connected by newly formed junctions between chromosomes called these.
What are chiasmata?
What does the presence of chiasmata indicate?
Crossing over may have occurred
The homologous chromosomes in this stage of prophase I condense and shorten to reach their maximum thickness, the nucleolus disappears, and the nuclear envelope disintegrates.
STEP 5
What is diakinesis?
How does metaphase I of meiosis differ from the metaphase of mitosis?
Paired homologous chromosomes (i.e., a tetrad) are aligned at the equatorial plate in meiosis instead of just individual chromosomes (i.e., a pair of sister chromatids)
Anaphase I and telophase I are similar to the same phases in mitosis EXCEPT in one manner. How do these phases differ from their meiotic counterparts?
The centromeres holding the sister chromatids together do not split; as such, the sister chromatids remain together
This process occurs because the maternal and paternal chromosomes of each pair are randomly aligned on one side or the other of the metaphase plate, thus contributing to genetic diversity. It can be see in ANAPHASE I & TELOPHASE I.
What is segregation or random assortment?
What is the key contribution of segregation (i.e., random assortment)?
Genetic diversity
At the completion of meiosis I, the cytoplasm divides. Each resulting daughter cell (a {…} spermatocyte or oocyte) is {…} (1n) in chromosome number and contains one member of each homologous chromosome pair. The cell is still {…} in DNA content (2d).
1) Secondary
2) Haploid
3) Diploid
An equatorial division that resembles mitosis.
What is meiosis II?
During meiosis II, the proteinase enzyme {…} cleaves the cohesion complexes between the sister chromatids.
Separase
How does cleavage of the cohesion complexes in the centromere region via separase affect the sister chromatids during anaphase II?
The cleavage allows sister chromatids to separate at anaphase II and move to opposite poles of the cell
During meiosis II, the cells pass through prophase II, metaphase II, anaphase II, and telophase II. These stages are essentially the same as those in mitosis, except that they involve a {…} set of chromosomes (1n) and produce daughter cells that have only {…} DNA content (1d).
1) Haploid
2) Haploid
Whereas cells produced by mitosis are genetically identical to the parent cell, the cells produced by meiosis are genetically…
Unique
What 2 factors determine the net rate of cell production?
The rates of cell proliferation and death
An abnormality in the cell proliferation rate can cause disorders referred to as these (e.g., hyperplasia, cancer, & autoimmune diseases).
What are disorders of cell accumulation?
An abnormality in the cell death rate can cause disorders referred to as these (e.g., atrophy, degenerative diseases, AIDS, & ischemic injury).
What are disorders of cell loss?
This type of cell death broadly refers to any cell death mediated by an intracellular death program, irrespective of the trigger mechanism or molecular machinery involved.
What is programmed cell death?
A cell’s internally encoded suicide program can be further divided into {…} cell death, which is controlled by {…} (enzymes) and preserves the integrity of cell membranes, and {…} cell death, which is a {…} process that likely compromises cell membrane integrity.
1) Apoptotic
2) Caspases
3) Nonapoptotic
4) Caspase-independent
This type of cell death occurs when cells are exposed to an unfavorable physical or chemical environment (e.g., hypothermia, hypoxia, radiation, low pH, cell trauma) that causes acute cellular injury and damage to the plasma membrane.
What is nonprogrammed cell death (i.e., necrosis)?
What are 2 key characteristics of necrosis?
Rapid cell swelling & lysis
What is the key difference in the processes of programmed vs. nonprogrammed cell death?
Programmed - physiological process driven by regulated intracellular signal transduction pathways
Nonprogrammed - pathological process of accidental cell death
Necrotic cell death is often associated with extensive surrounding tissue damage and an intense {…} response.
Inflammatory
How does the caspase enzyme affect cell size, membrane morphology, DNA integrity, and organelle function during apoptosis?
1) Cell shrinkage (in terms of volume)
2) Membrane blebbing (i.e., no membrane damage)
3) DNA fragmentation
4) Loss of organelle function
Apoptosis is characterized by controlled {…}, which maintains cell membrane {…}; thus, the cell “dies with dignity” without spilling its contents and damaging its neighbors.
1) Autodigestion
2) Integrity
These 2 types of cells and/or their secretions found in the immune system are toxic to other cells and initiate processes that destroy designated cells (e.g., cancer-transformed or virus-infected cells).
What are cytotoxic T lymphocytes & natural killer [NK] cells?
For example, cell death mediated by cytotoxic T lymphocytes, in which proteins called {…} and {…} are inserted into the plasma membrane, combines some aspects of both necrosis (alterations of plasma membrane) and apoptosis (stimulation of {…} enzyme).
1) Perforins
2) Granzymes
3) Caspase-3
During the loss of mitochondrial function associated with apoptosis, proteins from the mitochondrial intermembrane space, such as {…} and {…} (second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with low isoelectric point [pI]), are {…} into the {…} to activate a cascade of proteolytic enzymes called {…} that are responsible for dismantling the cell.
1) Cytochrome c
2) SMAC/DIABLO
3) Released
4) Cytoplasm
5) Caspases
The regulated release of cytochrome c and SMAC/DIABLO suggests that {…}, under the influence of regulatory {…} proteins, are the decision makers for initiating apoptosis.
1) Mitochondria
2) Bcl-2
What is the chief mechanism by which the mitochondria lose their function during apoptosis?
Changes in the permeability of the mitochondrial membrane channels prompts the loss of mitochondrial function
During apoptosis, what is one major alteration in the cell membrane that leads to membrane blebbing?
The translocation of certain molecules (e.g., phosphatidylserine) from the cytoplasmic surface to the outer surface of the plasma membrane
What is the final step of apoptosis that results in cell breakage?
Formation of apoptotic bodies
Why is it so difficult to find apoptotic cells in a routine H&E preparation?
NOTE: It has to do with the rate at which apoptosis occurs
Apoptosis occurs more than 20 times faster than mitosis, so these cells are just gone most of the time
A type of cell death that occurs during mitosis as a result from a combination of cellular damage and malfunction of several cell cycle checkpoints, such as the G1, S, and G2 DNA-damage checkpoints or the spindle-assembly checkpoint.
What is a mitotic catastrophe?
Apoptotic processes can be activated by a variety of {…} and {…} stimuli.
1) External
2) Internal
Some factors, such as {…} (TNF), acting on cell membrane receptors, trigger apoptosis by recruiting and activating the caspase cascade. Consequently, the TNF receptor (TNFr) belongs to the so-called {…} receptor family that can induce apoptosis.
1) Tumor necrosis factor
2) Death
A class of cysteine proteases that convey the apoptotic signal in a form of proteolytic cascade, with caspases cleaving and activating other caspases that then degrade other cellular targets that lead to cell death.
What are caspases?
Which 2 caspase proteases are on the upper end of the caspase cascade?
Caspase-8 & caspase-9
Which 3 caspase proteases are downstream effector caspases that cleave cellular targets?
Caspase-3, caspase-6, & caspase-7
Apoptosis is also activated by the insertion of pore-forming proteins {…} and {…} (serine proteases) into the cell membrane of virus-infected and/or virus-transformed cells by cytotoxic T lymphocytes.
1) Perforins
2) Granzymes
How does granzyme act on the caspase-3 enzyme to result in mitochondrial leakage of cytochrome c into the cell cytoplasm?
Granzyme acts directly on caspase-3, activating proapoptotic members of the Bcl-2 family, ultimately resulting in the mitochondrial leakage of cytochrome c into the cytoplasm
Internal activators of apoptosis include {…} (e.g., myc and rel), {…} suppressors such as p53, and {…} antimetabolites.
1) Oncogenes
2) Tumor suppressors
3) Nutrient-deprivation
List 4 events that accompany a mitotic catastrophe.
NOTE: Think about changes in chromatin, mitochondria, caspase enzyme, and DNA
1) Chromatin condensation
2) Mitochondrial release of cytochrome c
3) Caspase cascade activation
4) DNA fragmentation
Apoptosis can be inhibited by signals from other cells and the surrounding environment via these factors, including growth factors, hormones such as estrogen and androgens, neutral amino acids, zinc, and interactions with extracellular matrix proteins.
What are survival factors?
The functions of activated caspases are inhibited by the binding of {…} (IAPs), which are regulated by the proapoptotic SMAC/DIABLO complex.
Apoptosis inhibitors
This family of proteins is the most important regulatory function in apoptosis.
What is the Bcl-2 (B-cell lymphoma 2) family?
The proapoptotic members of the Bcl-2 family of proteins include {…} (Bcl-2–associated death promoter), {…} (Bcl-2–associated X protein), {…} (Blc-2 antagonist killer), {…} (Bcl-2–interacting domain), and {…} (Bcl-2–interacting mediator of cell death).
1) Bad
2) Bax
3) Bak
4) Bid
5) Bim
These 2 members of the Bcl-2 family of proteins are required to form apoptotic pores in the mitochondrial outer membrane to allow for the release of cytochrome c.
What are Bak & Bax?
What is the antiapoptotic member of the Bcl-2 family of proteins?
Bcl-xL (B-cell lymphoma-extra large)
How does Bcl-xL act as an antiapoptotic factor?
It blocks the action of Bax and Bak, preventing the release of cytochrome c and the subsequent activation of the caspase cascade
How do tumor cells acquire resistance to apoptosis? List 3 methods.
1) Expressing antiapoptotic proteins
2) Downregulating proapoptotic mediators
3) Mutating proapoptotic mediators
A cell detachment–induced apoptosis that prevents detached cells from further growth and reattachment to the extracellular matrix.
What is an anoikis?
How do defects in integrin signaling pathways lead to anoikis?
NOTE: Think about the function of integrin
Integrin works to anchor cell-to-ECM junctions, but defects in the signaling pathway trigger activation of the proapoptotic Bcl-2 family of proteins, which initiates apoptosis. A defect in integrin prevents the anchoring of cells to the ECM, which is, by definition, anoikis
In {…} cancer, cells develop mechanisms to survive the anoikis process, including changes in integrin receptor types, activation of antiapoptotic factors, oncogene activation, and growth factor receptor signaling.
Metastatic
This modality of programmed nonapoptotic cell death is a regulated cellular process that enables cells to recycle their contents through lysosomal degradation of their own components.
What is autophagy?
This is a nonapoptotic cell death process in which one cell can actively internalize a similar cell that became detached from the extracellular matrix.
What is entosis?
During entosis, following internalization, the “swallowed” cell remains alive within the host cell’s vacuole until it is either degraded by the {…} mechanism or {…}.
1) Lysosomal
2) Released
Entosis is a specific receptor-regulated process that involves {…} and the formation of anchoring cell-to-cell junctions between two similar types of cells (i.e., within the epithelium).
Cadherins
A nonspecific process observed in metastatic tumors that involves cancer cells “eating” and killing immune cells that are directed against them. IT IS COMPLETELY DIFFERENT FROM ENTOSIS.
What is cell cannibalism?
An alternative, nonapoptotic cell death that is induced by growth factor receptors (i.e., insulin growth factor [IGF-1] receptor).
What is paraptosis?
In contrast to apoptosis, the paraptosis modality of cell death is not mediated by caspases but by {…} (MAPKs).
Mitogen-activated protein kinases
This programmed nonapoptotic modality is a programmed process of fragmentation and fusion of the mitochondria with diminished production of adenosine triphosphate (ATP).
What is mitoptosis?
What is another term for mitoptosis?
Mitochondrial suicide
This programmed nonapoptotic modality is a form of cell death induced by infection with certain microorganisms that generates intense inflammatory reactions in immune cells.
What is pyroptosis?
Pyroptosis is uniquely dependent on the {…} enzyme, which is not involved in the caspase cascade in apoptotic cell death. Caspase-1 activates inflammatory cytokines such as {…} (IL-1) and {…} that mediate intense inflammatory reactions in surrounding tissue.
1) Caspase-1
2) Interleukin-1
3) IL-18
This programmed nonapoptotic modality is a unique form of cell death triggered by the presence of pathogens within neutrophils. Upon recognition of phagocytosed pathogens, some neutrophils modify their nuclear histone structures, resulting in chromatin decondensation and disruption of the nuclear membrane.
What is neutrophil extracellular trap-associated cell death (NETosis)?
NETosis leads to neutrophil death known as this.
What is suicidal NETosis?
The decondensed chromatin fibers and histones, combined with antimicrobial granular contents, form large webs of extracellular strands, which capture and kill a wide range of pathogens (e.g., bacteria, viruses, fungi, and parasites), referred to as these.
What are neutrophil extracellular traps?
This programmed nonapoptotic modality is a regulated caspase-independent cell death mechanism that can be induced in different cell types and is initiated by the activation of the TNFRs (or death receptors) and the Fas signaling pathway.
What is necroptosis?
A specific inhibitor of necroptosis that significantly reduces ischemic damage in affected tissues.
What is necrostatin-1?
What does it mean for different cell death modalities not to be isolated from each other?
This means that the different cell death modalities are capable of interacting with each other (e.g., apoptosis & necroptosis being activated by the death receptors)
