Cell as a Unit of Health and Disease

Question 1

study of of cellular abnormalities.

Answer 1

Modern Pathology

Question 2

variously function as enzymes, structural components, and signaling molecules and are used to assemble and maintain all of the cells in the body.

Answer 2

Genome Proteins-encoding Genes

Question 3

dispersed, transcriptionally active

Answer 3

euchromatin

Question 4

densely packed, transcriptionally inactive

Answer 4

heterochromatin

Question 5

centromeres act as the locus for the formation of a ____________ that regulates chromosome segregation at metaphase.

Answer 5

kinetochore protein complex

Question 6

repetitive nucleotide sequences that cap the termini of chromatids and permit repeated chromosomal replication without loss of DNA at the chromosome ends.

Answer 6

The telomeres

Question 7

chromatids are organized into short _______ (“ next letter in the alphabet ”) arms. The characteristic banding pattern of chromatids has been attributed to relative GC content (less GC content in bands relative to interbands), with genes tending to localize to interband regions.

Answer 7

“P” (“ petite ”) and long “Q”

Question 8

DNA wound around octameric histone cores

Answer 8

nucleosomes

Question 9

Promoters are noncoding regions of DNA that initiate gene transcription are located at?

Answer 9

they are on the same strand and upstream of their associated gene.

Question 10

The intronic sequences are subsequently spliced out of the _____ to produce the definitive message that is translated into protein—without the 3′- and 5′-untranslated regions (UTR).

Answer 10

pre-mRNA

Question 11

perhaps most, of the genetic variations ( polymorphisms ) associated with diseases are located in _________ regions of the genome.

Answer 11

non–protein-coding

Question 12

TRUE OF FALSE:

variation in gene regulation may prove to be more important in disease causation than structural changes in specific proteins.

Answer 12

TRUE

Question 13

Thus, person-to-person variation, including differential susceptibility to diseases and in response to environmental agents and drugs, is encoded in _____of our DNA.

Answer 13

less than 0.5%

Question 14

The two most common forms of DNA variation in the human genome are?

Answer 14

single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs)

Question 15

are variants at single nucleotide positions and are almost always biallelic

Answer 15

single-nucleotide polymorphisms (SNPs)

Question 16

SNPs occur across the genome—within?

Answer 16

exons, introns, intergenic regions, and coding regions.

Question 17

regions. Overall, about 1% of SNPs occur in

Answer 17

coding regions,

Question 18

TRUE OR FALSE:

In other instances, the SNP may be a “neutral” variant that has no effect on gene function or carrier phenotype.

Answer 18

TRUE

Question 18

TRUE OR FALSE:

In other instances, the SNP may be a “neutral” variant that has no effect on gene function or carrier phenotype.

Answer 18

TRUE

Question 19

even ________ may be useful markers if they happen to be co-inherited with a disease-associated gene as a result of physical proximity.

Answer 19

“neutral” SNPs

Question 20

other words, the SNP and the causative genetic factor are in

Answer 20

linkage disequilibrium.

Question 21

CNVs are a more recently identified form of genetic variation consisting of different numbers of large contiguous stretches of DNA from 1000 base pairs to millions of base pairs.

Answer 21

copy number variations - CNVs

Question 22

are responsible for between 5 and 24 million base pairs of sequence difference between any two individuals.

Answer 22

CNVs

Question 23

TRUE OR FALSE:

We currently know much less about CNVs than SNPs, therefore their influence on disease susceptibility is less established.

Answer 23

TRUE

Question 24

heritable changes in gene expression that are not caused by alterations in DNA sequence.

Answer 24

epigenetics,

Question 25

Such cell type-specific differences in DNA transcription and translation depend on _______ (literally, factors that are “above genetics”)

Answer 25

epigenetic factors

Question 26

consist of DNA segments 147 base pairs long that are wrapped around a central core structure of highly conserved low molecular weight proteins called histones

Answer 26

Nucleosomes

Question 27

a central core structure of highly conserved low molecular weight proteins called ___

Answer 27

histones

Question 28

The resulting DNA-histone complex resembles a series of beads joined by short DNA linkers and is generically called

Answer 28

chromatin

Question 29

nuclear chromatin exists in two basic forms: (1) cytochemically dense and transcriptionally inactive ________ and (2) cytochemically dispersed and transcriptionally active _______

Answer 29

heterochromatin ; euchromatin

Question 30

______ can reposition nucleosomes on DNA, exposing (or obscuring) gene regulatory elements such as promoters. “

Answer 30

chromatin remodeling complexes c

Question 31

carry out more than 70 different histone modifications generically denoted as marks

Answer 31

Chromatin writer” complexes

Question 32

Actively transcribed genes in euchromatin are associated with ________ that make the DNA accessible to RNA polymerases.

Answer 32

histone marks

Question 33

______ have histone marks that enable DNA compaction into heterochromatin.

Answer 33

inactive genes

Question 34

Histone marks are reversible through the activity of “chromatin erasers.”

Question 35

Histone marks are reversible through the activity of

Answer 35

“chromatin erasers.”

Question 36

binding histones that bear particular marks and thereby regulating gene expression.

Answer 36

“chromatin readers,”

Question 37

Both lysines and arginines can be methylated by specific writer enzymes; in particular, methylation of lysine residues in histones may be associated with either transcriptional activation or repression, depending on the histone residue that is “marked”.

Answer 37

Histone methylation

Question 38

. Lysine residues are acetylated by histone acetyl transferases (HAT), whose modifications tend to open up the chromatin and increase transcription. In turn, these changes can be reversed by histone deacetylases (HDAC), leading to chromatin condensation.

Answer 38

Histone acetylation

Question 39

Serine residues can be modified by phosphorylation; depending on the specific residue, the DNA may be opened up for transcription or condensed to become inactive.

Question 39

Serine residues can be modified by phosphorylation; depending on the specific residue, the DNA may be opened up for transcription or condensed to become inactive.

Answer 39

Histone phosphorylation .

Question 40

________ High levels of DNA methylation in gene regulatory elements typically result in transcriptional silencing. Like histone modifications, DNA methylation is tightly regulated by methyltransferases, demethylating enzymes, and methylated-DNA-binding proteins.

Answer 40

DNA methylation.

Question 41

__________- Much less is known about these proteins, which are believed to bind to noncoding regions and control long-range looping of DNA, which is important in regulating the spatial relationships between gene enhancers and promoters that control gene expression.

Answer 41

Chromatin organizing factors.

Question 42

histone H1 sits on the_____ between nucleosomes and helps stabilizes the overall chromatin architecture.

Answer 42

20-80 nucleotide linker DNA

Question 43

The histone subunits are _____- charged, thus allowing the compaction of the negatively charged DNA.

Answer 43

positively charged

Question 44

Certain marks such as _______ “open up” the chromatin structure

Answer 44

histone acetylation

Question 45

tends to condense the DNA and leads to gene silencing.

Answer 45

methylation of particular histone residues,

Question 46

many epigenetic alterations (e.g., histone acetylation and DNA methylation) are ____________

Answer 46

reversible and are amenable to therapeutic intervention

Question 47

many epigenetic alterations (e.g., histone acetylation and DNA methylation) are ____________

Answer 47

reversible and are amenable to therapeutic intervention

Question 48

are already being tested in the treatment of various forms of cancer.

Answer 48

HDAC inhibitors and DNA methylation inhibitors

Question 49

encoded by genes that are transcribed but not translated.

Answer 49

noncoding RNAs.

Question 50

_________ do not encode proteins; instead, they function primarily to modulate the translation of target mRNAs into their corresponding proteins.

Answer 50

The miRNAs

Question 51

_____ by miRNA is a fundamental and well-conserved mechanism of gene regulation present in all eukaryotes (plants and animals)

Answer 51

Posttranscriptional silencing of gene expression

Question 52

By current estimates, the human genome encodes approximately _______ , some _________ the number of protein-coding genes.

Answer 52

1000 miRNA genes ; 20-fold less than

Question 52

By current estimates, the human genome encodes approximately _______ , some _________ the number of protein-coding genes.

Answer 52

1000 miRNA genes ; 20-fold less than

Question 53

generates mature single-stranded miRNAs of 21 to 30 nucleotides that are associated with a multiprotein aggregate called RNA-induced silencing complex

Answer 53

enzyme DICER.

Question 54

Subsequent base pairing between the miRNA strand and its target mRNA directs the ____ to either induce mRNA cleavage or repress its translation.

Answer 54

RISC

Question 55

All mRNAs contain a so-called ______ in their 3′ untranslated region (UTR) that determines the specificity of miRNA binding and gene silencing. In this way, the target mRNA is posttranscriptionally silenced

Answer 55

seed sequence

Question 56

are short RNA sequences that can be introduced experimentally into cells. These serves as substrates for Dicer and interact with the RISC complex in a mannaer analogous to endogenous miRNAs.

Answer 56

Small interfering RNAs (siRNAs)

Question 57

Synthetic siRNAs targeted against specific mRNA species have become useful laboratory tools to study gene function (so-called _____);

Answer 57

knockdown technology

Question 58

they are also being developed as possible therapeutic agents to silence pathogenic genes, such as oncogenes involved in neoplastic transformation.

Answer 58

Synthetic siRNAs targeted against specific mRNA

Question 59

number of lncRNAs may exceed coding mRNAs by ___.

Answer 59

10- to 20-fold

Question 60

transcribed from the X chromosome and plays an essential role in physiologic X chromosome inactivation.

Answer 60

XIST

Question 61

_____itself escapes X inactivation, but forms a repressive “cloak” on the X chromosome from which it is transcribed, resulting in gene silencing.

Answer 61

XIST

Question 62

can facilitate transcription factor binding and thus promote gene activation.

Answer 62

(lncRNAs)

Question 63

can preemptively bind transcription factors and thus prevent gene transcription.

Answer 63

lncRNAs

Question 64

may act as scaffolding to stabilize secondary or tertiary structures and/or multi-subunit complexes that influence general chromatin architecture or gene activity.

Answer 64

lncRNAs

Question 65

The viability and normal activity of cells depend on a variety of fundamental housekeeping functions that all differentiated cells must perform. These functions include:

Answer 65

protection from the environment, nutrient acquisition, communication, movement, renewal of senescent molecules, molecular catabolism , and energy generation

Question 66

Many normal housekeeping functions are compartmentalized within____

Answer 66

membrane-bound intracellular organelles

Question 67

_____ allows the creation of unique intracellular environments (e.g., low pH or high calcium) that may then selectively regulate the function of enzymes or metabolic pathways.

Answer 67

compartmentalization

Question 68

New proteins destined for the plasma membrane or points beyond are synthesized in the __________

Answer 68

rough endoplasmic reticulum (RER)

Question 69

New proteins destined for the plasma membrane or points beyond are synthesized in the rough endoplasmic reticulum (RER) and physically assembled in the ___________

Answer 69

Golgi apparatus ;

Question 70

proteins intended for the cytosol are synthesized on

Answer 70

free ribosomes.

Question 71

may be abundant in certain cell types such as gonads and liver where it is used for steroid hormone and lipoprotein synthesis, as well as for the modification of hydrophobic compounds (for example, drugs) into water-soluble molecules for export.

Answer 71

Smooth endoplasmic reticulum (SER)

Question 72

____ are intracellular organelles that contain degradative enzymes that permit the digestion of a wide-range of macromolecules, including proteins, polysaccharides, lipids, and nucleic acids.

Answer 72

Lysosomes

Question 73

_______ are a specialized type of “grinder” that selectively chews up denatured proteins, releasing peptides. In some cases the peptides so generated can be presented in the context of class I major histocompatibility molecules

Answer 73

Proteasomes

Question 74

_______ play a specialized role in the breakdown of fatty acids, generating hydrogen peroxide in this process.

Answer 74

Peroxisomes

Question 75

shuttle internalized material to the appropriate intracellular sites or direct newly synthesized materials to the cell surface or targeted organelle.

Answer 75

Endosomal vesicles

Question 76

Cell movement—both organelles and proteins within the cell, as well as movement of the cell in its environment—is accomplished through the

Answer 76

cytoskeleton

Question 77

also serve as an important source of metabolic intermediates that are needed for anabolic metabolism; they are sites of synthesis of certain macromolecules (e.g., heme), and contain important sensors of cell damage that can initiate and regulate the process of programmed cell death.

Answer 77

mitochondria

Question 78

fluid bilayers of amphipathic phospholipids with hydrophilic head groups that face the aqueous environment and hydrophobic lipid tails that interact with each other to form a barrier to passive diffusion of large or charged molecules

Answer 78

Plasma membranes

Question 79

___ on the ____membrane leaflet can be phosphorylated, serving as an electrostatic scaffold for intracellular proteins

Answer 79

Phosphatidylinositol ; inner

Question 80

is normally restricted to the inner face where it confers a negative charge involved in electrostatic protein interactions; however, when it flips to the extracellular face, which happens in cells undergoing apoptosis (programmed cell death), it becomes an “eat me” signal for phagocytes. In the special case of platelets, it serves as a cofactor in the clotting of blood.

Answer 80

Phosphatidylserine

Question 81

___- are preferentially expressed on the extracellular face; glycolipids (and particularly gangliosides, with complex sugar linkages and terminal sialic acids that confer negative charges) are important in cell-cell and cell-matrix interactions, including inflammatory cell recruitment and sperm-egg interactions.

Answer 81

Glycolipids and sphingomyelin

Question 82

___ are overrepresented in the outer leaflet, and ____ found on the inner leaflet;

Answer 82

phosphatidylcholine and sphingomyelin ; phosphatidylserine (negative charge) and phosphatidylethanolamine are predominantly

Question 83

glycolipids occur only on the ___ face where they contribute to the extracellular glycocalyx.

Answer 83

outer

Question 84

The phospholipid distribution within the membrane is asymmetric due to the activity of

Answer 84

flippases

Question 85

certain membrane components have a predilection for association through horizontal interactions in the bilayer, which leads to the creation of distinct lipid domains known as

Answer 85

“lipid rafts.”

Question 86

The plasma membrane is liberally studded with a variety of proteins and glycoproteins involved in __

Answer 86

(1) ion and metabolite transport
(2) fluid-phase and receptor-mediated uptake of macromolecules, and
(3) cell-ligand, cell-matrix, and cell-cell interactions.

Question 87

Most proteins are _____, having one or more relatively hydrophobic α-helical segments that traverse the lipid bilayer.

Answer 87

integral or transmembrane proteins

Question 88

TRUE OR FALSE:

Integral membrane proteins typically contain positively charged aminoacids in their cytoplasmic domains, which anchor the proteins to the negatively charged head groups of membrane phospholipids.

Question 88

TRUE OR FALSE:

Integral membrane proteins typically contain positively charged aminoacids in their cytoplasmic domains, which anchor the proteins to the negatively charged head groups of membrane phospholipids.

Answer 88

TRUE

Question 89

Proteins may be synthesized in the___ and posttranslationally attached to ___groups that insert into the ___ side of the plasma membrane.

Answer 89

cytosol ; prenyl ; cytosolic

Question 90

Insertion into the membrane may occur through ___ anchors on the extracellular face of the membrane.

Answer 90

glycosylphosphatidylinositol (GPI)

Question 91

____ may noncovalently associate with true transmembrane proteins.

Answer 91

Peripheral membrane proteins

Question 92

Many plasma membrane proteins function together as large complexes; these may either be aggregated under the control of ____ or by ___ in the plasma membrane followed by complex formation in situ.

Answer 92

chaperone molecules in the RER ; lateral diffusion

Question 93

unique membrane domains can be generated by the ___

Answer 93

interaction of proteins with cytoskeletal molecules or extracellular matrix.