Cell Cycle Division and Stem Cells Flashcards
The easily visible processes of nuclear division (mitosis) and cell division (cytokinesis), are collectively called (blank).
M phase
the M phase typically occupies how much time of the cell cycle?
a small fraction
What are the 5 stages of mitosis?
prophase, metaphase, anaphase, telophase, cytokinesis
An abrupt change in the biochemical state of the cell occurs from (blank) to (blank).
metaphase to anaphase
A cell can pause in metaphase before the transition to anaphase, but once the point has been passed, the cell carries on to the end mitosis and through (blank)
cytokinesis into interphase
Where does DNA replication occur?
interphase
The part of interphase where DNA is replicated is called (blank)
S phase
The cell grows continually in (blank) which consists of three phases.
interphase
DNA replication is confined to S phase; (blank) is the gap between the M phase and S phase.
G1
(Blank) is the gap between S phase and M phase.
G2
When does the nucleus and the cytoplasm divide
M phase
Which phase of interphase ensures DNA has been replicated correctly and that each daughter cell will be able to get an equal amount of DNA?
G2 phase
Interphase is everything but (blank).
M phase
In meiosis, after DNA replication, 2 nuclear ( and cell) division are required to produce (blank) gametes.
haploid
Each diploid cell that enters meiosis therefore produces four (blank) different haploid cells.
genetically
Each diploid cell that divides by mitosis produces two genetically (blank) diploid cells.
identical
(Blank) starts at the end of G2 and ends at the start of the next G1 phase. It includes the five stages of nuclear division (mitosis), as well as cytoplasmic division (cytokinesis).
M phase
In the breakdown of the nuclear envelope what is biochemically happening?
phosphorylation of lamins
Mitosis involves chromosomal (blank)
condensation
Mitosis involves ER and Golgi (blank).
fragmentation
In mitosis, the cell loosens (blank) adhesions.
extracellular
In mitosis, (blank) is transformed to bring about organized movements of chromosomal segregation.
cytoskeleton
In mitosis, The number of proteins that are thought to be (blank) are thought to be large – every part of the cell is affected in some way.
phosphorylated
Chromatids are bound together by multisubunit protein complexes called (blank).
cohesins.
what crosslinks two adjacent sister chromatids, gluing them together.
cohesins
A typical mitotic chromosome, structure will look like what?
gently coiled scaffold along each of the two chromatids. Looks like an exclamation point!
A metaphase chromosome from a cell artificially blocked in metaphase; in the chromosomes of these cells, what has happened?
the scaffold has condensed by further helical folding. Looks like an X
Cohesions and condensins hold sister chromatids together by (blank) binding regions and a hinge.
DNA and ATP
What introduces positive superhelical tension into DNA in an ATP-hydrolysis-dependent manner
condensin
What is a protein complex that regulates the separation of sister chromatids during cell division, either mitosis or meiosis.
Cohesin
What allows for the dimerization of the SMCs od condensin or cohesin dimers?
A hinge domain
Once cohesin dimers are bound by ATP, what happens? Why is this important?
It forms a ring structure.
Important because the ring surrounds the chromosomes which facilitates spindle attachment onto chromosome
What are the 2 cytoskeleton machines that operate in M phaes?
Assembly of mitotic spindle (segregates chromosomes)
Contractile ring assembles and divides the cell in two
The mitotic spindle and contractile ring are two distinct (blank) structures that appear transiently during M phase.
cytoskeleton
The (blank) is the principle Microtubule Organizing Center.
centrosome
microtubules are nucleates in the centrosome at their (-) ends. (+)ends grow which way from the cell.
outward
Before a cell divides it must (blank) its centrosome to provide one for each daughter cell.
duplicate
The (blank) consists of a centriole pair and associated matrix.
centrosome
In (blank), the two centrioles separate.During S phase, a (blank) begins to grow near the base of each mother centriole and at a right angle to it.The elongation of the daughter centriole is usually completed by what phase? The two centriole pairs remain close together in a single centrosomal complex until the beginning of (blank) when the complex splits in two. Each centrosome now nucleates its own radial array of microtubules called an (blank)
G1 daughter centriole G2 M phase Aster
At (blank), the nuclear envelope breaks down, allowing the spindle microtubules to interact with the fully condensed chromosomes.
prometaphase
During (blank), the centrosome (not visible) forms the focus for the interphase microtubule array
interphase
By early (blank), the single centrosome contains two centriole pairs (not visible). At (blank), the centrosome divides, and the resulting two asters can be seen to have moved apart.
prophase
late prophase
At (blank), the bipolar structure of the spindle is clear, and all the chromosomes are aligned at the equator of the spindle.
metaphase
At (blank), the sister chromatids all separate synchronously and, under the influence of the microtubules, the daughter chromosomes begin to move toward the poles.
early anaphase
By (blank), the spindle poles have moved farther apart, increasing the separation of the two groups of chromosomes.
late anaphase
At telophase, the daughter nuclei re- form, and by (blank), cytokinesis is almost complete, with the midbody (discussed later) persisting between the daughter cells.
late telophase
Which of the following isn’t true?
a)Mitosis must ensure that all the essential classes of cell components are inherited by each daughter cell.
b) Organelles like mitochondria cannot assemble spontaneously. They arise from growth and fission of existing organelles.
c) Similar to mitochondria, for ER and Golgi. Thus daughter cells must inherit at least one of these structures.
d) Golgi and ER break up into a set of smaller fragments and vesicles so that they can be more evenly distributed when the cell divides.
e) ER vesicles seem to associate with microtubules of the mitotic spindle and the spindle may help them become distributed.
f) all are true
f) all are true
What are the three classes of microtubules?
astral, kinetochore, overlap microtubules
where are the minus ends of microtubules anchored?
at the spindle poles
Do most of the kinetochore and overlap microtubules get released from the centrosome? How do they stay near the spindle poles?
yes, motor proteins.
Microtubules in an (blank) cell are much more dynamic, on average, than the microtubules at interphase.
M phase
½ life of microtubules in (blank) decreases 20 fold compared to interphase.
Metaphase
What initiates the changes of microtubule length by causing the phosphorylation of
Microtubule associated proteins (MAPS) and Catastrophins
M-Cdks.
MAPS and Catastrophins have opposite effects on (blank)
microtubule polymerization.
The balance between (blank) and (blank) influences the frequency of microtubule catastrophes(disasters) and microtubule length.
Maps and catastrophins
(blank) motor proteins operating on interacting antiparallel microtubules help separate the two poles of a forming mitotic spindle.
Plus-end-directed
When two microtubules from opposite centrosomes interact in an overlap zone, plus-end-directed, kinesin-related motor proteins (blank) the microtubules together and tend to drive the microtubules in the direction that will push the centrosomes apart
cross link
Minus-end- directed dynein motors associated with the nuclear envelope are also thought to help separate the two centrosomes by pulling on the two sets of (blank).
astral microtubules
What specifies the construction of the kinetochore?
DNA sequence at centromere
Kinetochores assemble on centromeres during (Blank)
late prophase
The number of microtubules bound to a kinetochore is over (blank) in mammalian cells.
40
Anaphase A depends on motor proteins operating at the kinetochores that, together with the (blank) of the kinetochore microtubules, pull the daughter chromosomes toward the nearest pole.
depolymerization
Two separate forces are thought to be responsible for (blank). The elongation and sliding of the overlap microtubules past one another in the central spindle push the two poles apart, and outward forces exerted by the astral microtubules at each spindle pole act to pull the poles away from each other, toward the cell surface.
anaphase b
What process does this describe?
- Dephosphorylation of nuclear lamins results in reassembly of the lamina that bind to vesicles of the nuclear envelope membrane that fuse around groups of chromosomes.
- Chromosomes come together and the membranes fuse to form a single nuclear envelope.
- Proteins that contain nuclear localization signals are imported, all others are excluded.
- Nuclear pore complexes also reform.
- Chromosomes decondense and RNA synthesis resumes.
REASSEMBLY OF DAUGHTER NUCLEI
What is the mechanism in the cleavage furrow?
contractile ring of actin and myosin filaments
DNA replication, mitosis, and cytokinesis are triggered by a (blank)
cell-cycle control system
What are the two key components of the cell-cycle control system?
cyclin-dependent kinase (Cdk) and cyclin
What rises and falls as the cell progresses through the cell cycle which leads to cyclic changes in the phosphorylation of intracellular proteins that initiate or regulate the events of the cell cycle?
Cdk’s
Cyclic changes in Cdk activity are controlled by a complex array of enzymes and proteins, the most important are (blank)
cyclins
Cyclin proteins do not simply activate Cdk’s but also drive them to (blank). Each cyclin/Cdk complex phosphorylates a different set of target proteins.
specific target proteins
The active cyclin–Cdk complex is turned off when phosphorylated by the (blank).
Removal of these phosphates by the phosphatase Cdc25 results in activation of the cyclin–Cdk complex. The activating phosphate is added by CAK.
Wee1 kinase
CYCLIN-CDK COMPLEXES ARE ALSO REGULATED BY THE BINDING OF what inhibitor proteins?
CKI (CDK INHIBITOR PROTEINS )
(blank) are primarily involved in the control of the G1 and S phases.
(blank) binding rearranges the structure of the CDK site rendering it inactive.
CKI’s
CKI’s (CDK inhibitor proteins)
Cell cycle control system is also dependent upon cyclic (blank)
proteolysis
Cyclin/CdK complexes are inactivated by regulated (blank) of cyclins at different times of the cycle. Cyclin destruction occurs by a (blank)-dependent process. The rate limiting step in cyclin destruction is in the final (blank) transfer step by enzymes known as ubiquitin ligases.
proteolysis, ubiquitin, ubiquitin
What two ligases are important in the breakdown of cyclins and other cell regulators?
In G1 and S phase= SCF
In M Phase= AMP
The (blank) of a target protein, such as the CKI, allows it to be recognized by SCF, which is constitutively active and constant through the cell cycle. With the help of two additional proteins called (blank) , SCF serves as a (blank)
, transfering multiple ubiquitin molecules onto the CKI protein. The ubiquitylated CKI protein is then immediately recognized and degraded in a proteasome
phosphorylation
E1 and E2
ubiquitin ligase
Active (blank) allows for dedragation of M-cyclin.
APC
M- cyclin ubiquitylation is performed by (blank), which is activated in late mitosis by the addition of an activating subunit to the complex (Cdc20).
Anaphase Promoting Complex (APC)
Each of the cyclin/CdK complexes serves as a (blank) that triggers a specific cell-cycle event.
molecular switch
HOw often does the initiation of DNA replication occur?
once per cell cycle
THe origin of recognition complex (ORC) ermains associated with the (blank) throughout the cell cycle.
replication origin
In (blank) the regulatory protein Cdc6 associates with ORC. Aided by Cdc6, Mcm ring complexes then assemble on the adjacent DNA, resulting in the formation of the pre-replicative complex.
In G1,
(blank) then triggers origin firing, assembling DNA polymerase, activating the Mcm protein rings to migrate along DNA strands as DNA helicases. It can also block re-replication by causing dissociation of Cdc6 from ORC and its degredation.
The S-Cdk
Disassociation of Cdc6 causes the breakdown of the pre-RC (pre-replicative complex).
s-Cdk (blank) Cdc6, causing Cdc6 ubiquitylation by SCF. As a result any Cdc6 protein not bound to ORC is quickly degraded.
S-Cdk also (blank) Mcm proteins and triggers transport out of the nucleus.
Mcm cannot reset an ORC-containing origin for DNA replication until M-Cdk has been inactivated at the end of mitosis.
phosphorylates
phosphorylates
Several (blank) cooperate to restrain pre-RC from DNA re-replication.
cyclin-Cdk complexes
S-Cdk activity remains high during (blank) and early mitosis preventing re-replication from occurring after completion of the s-phase.
M-Cdk also ensures that re-replication does not occur during (blank) by phosphorylating Cdc6 and Mcm proteins.
G2
Mitosis
(blank) detect unreplicated DNA and block the activation of MCdk.
Sensor mechanisms
Cdk1 associates with M-cyclin as the levels of M-cyclin gradually rise. The M-Cdk complex is phosphorylated by Cdk-activating kinase (CAK) and on inhibitory sites by Wee1 kinase. The inactive M-Cdk complex (due to wee-1) is then activated at the end of G2 by the phosphatase (blank). Cdc25 is stimulated in part by Polo and is further stimulated by active M-Cdk which is a (blank) mechanism. This feedback is enhanced by the ability of M-Cdk to inhibit (blank).
Cdc25
+ve feedback
Wee 1
What does this?
i) Induce assembly of the mitotic spindle.
ii) Insure the replicated chromosomes attach to the spindle.
iii) Possibly cause chromosomal condensation, nuclear envelop breakdown, actin cytoskeletal rearrangement, reorganization of the Golgi and ER.
M-Cdk
The requirements for protein degredation to exit from mitosis are:
1) Blank
2) Blank
proteolysis (for sep of sister chromatids)
M-cyclin
Cohesin cleavage by separase is facilitated by the (blank) of the cohesin complex adjacent to the cleavage site, just before anaphase begins.
phosphorylation
When securin and inactive separase are bound what happens?
sisterchromatids cannot separate into anaphase
How is securin ubiquitilized and degraded so anaphase can continue?
APC is activated by Cdc2
When cells are in M-phase are Sic1 and Hct 1 active or inactive
WHen cells are in G1 are Sic1 and Hct 1 active or inactive
When cells are in S phase Sic1 and Hct 1 active or inactive
inactive, active, inactive
What tells Sic 1 and Hct 1 to inactivate at the end of G1 phase?
the rise ins S-Cdk levels
G1-CdK intiates RB phosphorylation which inactivates it, this inactivateion activates E2F to activate S phase genes. This creates an increase in (blank). This new genes tell Rb to do what?
E2F acts back to stimulate the transcipriton of what?
G1/s-cyclin (cyclin E) and S-cyclin (Cyclin A)
keep getting phosphoryalted (+ve feedback)
Itself (positive feedback loop for itself)
How does DNA damage arrest the cell cycle in G1?
activation of protein kinases that phosphorylate p53
Mdm2 bind p53 -> destruction. Phosphrylation of p53 blocks (blank) binding. P53 accumlates and stimulates transcription of CKI protein (blank). p21 binds and inactivates G1/s-Cdk and S-Cdk complex which arrests cell in G1.
Mdm2
p21
The core of the cell-cycle control system consists of a series of (blank). The activity of each complex is also influenced by various inhibitory checkpoint mechanisms, which provide information about the extracellular environment, cell damage, and incomplete cell-cycle events (top). These mechanisms are not present in all cell types; many are missing in early embryonic cell cycles.
cyclin-Cdk complexes
Activation of cell- surface receptors leads to the activation of (blank), which promotes protein synthesis, at least partly through the activation of eIF4E and S6 kinase. Growth factors also inhibit protein breakdown.
PI 3-kinase
Growth factors control:
(i) Regulation of cell growth or division.
(ii) Proliferation of cells.
(iii) Survival.
(iv) Migration.
(v) Physiological function of cells.
What does growth factors stimulate PI-3 kinase to do?
Activate elF4E and S6 Kinase to increase mRNA translation and stimulation of cell growht
Myc is a (blank) with max.
heterodimer
Dr. Ward talked about salamanders and how their ploidy number is proprotional to cell size. What was the main point about this story?
that cell mass is regulated because the organisms and organs were the same size even though they had different number of cells (smaller number of cells,greater cell mass)
What are the 4 essential processes by which a multicellular organism is made?
(i) CELL PROLIFERATION
(ii) CELL SPECIALIZATION
(iii) CELL INTERACTION
(iv) CELL MOVEMENT
Cells differ NOT because they contain different genetic information, but because they (blank). (blank) controls the 4 essential processes by which the embryo is created.
express different sets of genes
Selective gene expression
The genes a cell expresses and the way that it behaves depend upon the cells (blank).
past as well as its present environment.
Cells maintain their specialized characters not because they continually receive the same instructions from their surroundings.
Cells retain a record of signals from where?
from their ancestors, received in early embryonic environment.
A fertilized egg divides to produce a (blank)—a hollow sphere of epithelial cells surrounding a cavity.
blastula
The cells expressing Tbx5 will form a wing; those expressing Tbx4 will form a leg. (blank) code for related gene regulatory proteins, which are thought to dictate which type of limb develops.
Tbx4 and Tbx5
What are two ways of making sister cells different?
Asymmetric cell division and inductive interactions
What is it called when molecules are divided unequally between daughter cells. These molecule(s) acts as a determinant (directly or indirectly) for one of the cell fates.
Asymmetric cell division
What interactions produce daughter cells by influences of adjacent cells
Inductive interactions
What is it called when sister cells become different as result of influences acting on them after birth?
symmetric division
What are the most common form of interactions.
The signals are usually limited to time and space.
Inductive interactions
What are 2 ways to create a morphogen gradient?
By localized production of an inducer (morphogen) that diffuses away from its source.
By localized production of an inhibitor that diffuses away from its source and blocks that action of uniformly distributed inducer
a (blank) is a signaling molecule that acts directly on cells to produce specific cellular responses depending on its local concentration.
morphogen
What make up a large number of developmental decisions?
extracellular inhibitors
A series of inductive interactions can generate many types of cells, starting from only a few. (blank) set the levels where cells can be influenced by morphogens.
Thresholds
Fertilization triggers 2 types of intracellular movements.
What are they?
1) cell cortex rotation through 30o relative to the core of the egg in a direction determined by sperm entry.
2) Active transport of Dishevelled protein, a component of the Wnt signaling pathway.
What results Dorsal concentration of (blank) protein defines the dorsoventral polarity of a the embryo?
dishevelled
What do treatments have to block to produce embryos with no dorsoventral symmentry?
cortical rotation
What are the four main movements during gastrulation?
1) animal pole epithelium expands
2) mesodermal cells migrate over fibronectin
3) bottle cells help force curvature of invaginating epithelium
4) marginal zone undergoes convergent extension
What is the main driving force of cell movement during gasatrulation?
convergent extension
What becomes thinner as it expands in gastrulation?
the animal pole epithelium
What helps pull the invaginated tissues forward in cell movement during gastrulation?
migration of mesodermal cells over a fibronectin rich matrix
Mammalian embryo development is highly (blank).
Individual cells in the inner mass are initially (blank).
REGULATIVE
totipotent
Less than a week after human egg is fertilizes, the devoloping embryo contains about 100 to 150 cells that have yet (blank)
differentiatied
The embryo is a hollow ball, called a (blank) consisting of an outer cell mass (placenta), and an inner cell mass (ICM), which would become the fetus.
blastocyst,
The embryo, called a (blank) at
14-16 days, would contain three distinctive germ layers whose descendants would ultimately form hundreds of different tissue types in the human body.
gastrula
What is this?
- It is not itself terminally differentiated (that is, it is not at the end of a pathway of differentiation).
- It can divide without limit (or at least for the lifetime of the animal).
- When it divides, each daughter has a choice: it can either remain itself, or it can embark on a course that commits it to terminal differentiation
stem cell
What are the three properties of stem cells
Self renewal, potency (can differentiate into specialized cell), can be totipotent or pluripotent
What is this:
Ability of a single cell to divide and produce ALL of the cells in the body. Classical example is the zygote and represents the cell with the greatest differentiation potential. Following fertilization the development of the morula (16 cell stage) start to differentiate during gastrulation.
totipotency
What is this:
Typically refers to a stem cell possessing the potential to divide into any of the three germ layers.
pluripotent
What is this:
Induced pluripotent stem cells which are artificially derived from an non-pluripotent cell (somatic cell).
iPS cells
What are we discussing:
*Induced by forcing somatic cells to express certain genes and transcription factors.
*The ability to induce a somatic cell (fibroblast) into a pluripotent state was first reported in 2006: The 4 factors were: Oct4, Sox2, Klf4 and c-Myc.
Human (blanks) were achieved in 2007 from dermal fibroblasts.
(blanks) possess similar traits to ESCs but do not require the use of embryos.
iPSCs
(blank) stem cells recovered from the placenta and umbilical cord. Mesenchymal stem cells are used for immune suppression and inflammatory conditions.
Allogenic
(blank) cells are mobilized and recovered for autologus transplantation for applications, including cancer, blood diseases, stroke and multiple sclerosis
Bone marrow
(blank) stem cells are of fetal origin or differentiated from embryonic stem (ES) cells and induced pluripotential stem (iPS) cells. Both ES and iPS cells are poised for clinical trials for repair of spinal injury, macular degeneration, diabetes and cancer.
neural
What were found to be turmorigenic and have limited their use in clinical trials in the US?
iPSCs
It has been suggested that (blank) cells are totipotent or at least multipotent do to somatic expression of combined transcription factors that directly induce other defined cell fates.
all
What are these and where are all these found?
- (blank) cells - brush border cells
or enterocytes. - (blank) cells (as in respiratory epithelium)
secrete mucus. - (blank) cells form part of the innate
immune defense system. - (blank) cells, of more than
15 different subtypes, secrete serotonin
and cholecystokinin (CCK).
Stem cells in the gut
1) absorptive
2) Goblet cells
3) Paneth cells
4) Enteroendocrine cells
Four differentiated cell types found in the epithelial lining of the small intestine are what and All are generated from undifferentiated multipotent stem cells at the base of the (blank).
1) absorptive
2) Goblet cells
3) Paneth cells
4) Enteroendocrine cells
crypts
What control the production of differentiated cells from stem cells in the intestine?
Wnt and Notch signaling
(blank) signaling maintains proliferation in the crypt
Wnt signaling in the crypt drives expression of the components of the (blank) in that region; Notch signaling is thus active in the crypt and, through lateral inhibition, forces cells there to (blank) .
Wnt
Notch signaling pathway
diversify
What 2 pathways must be activated in
the same cell to keep it as a stem cell in the intestine. The progeny of the stem cell continue dividing under the influence of Wnt even after they become committed to a differentiated fate.
Wnt and Notch
Mutations in the (blank) gene lead to colonic adenoma
APC
Mutations in APC gene lead to (blank)
colonic adenoma
A mutation in the APC gene has given rise to a clone of cells that behave as though the (blank) signaling pathways is permanently activated. Which makes these cels from an adenoma (an enormous, steadily expanding mass of giant cryptlike structure)
Wnt
