13). Q&A: Cell Cycle Regulation and Growth Control

Flashcards reviewing lecture notes on Cell Cycle Regulation and Growth Control by Cristine Smoczer MD, PhD.

Who presented the lecture on Cell Cycle Regulation and Growth Control?

Cristine Smoczer MD, PhD.

What are the three primary reasons why cells undergo division?

Growth (need for more cells), replacement (maintenance of normal tissue), and tissue repair/wound healing (replacement of damaged cells).

Which cell types are terminally differentiated and never divide?

Neurons, myocytes, and osteocytes.

Which cell types are reversibly quiescent and divide only rarely when needed?

Stem cells, hepatocytes, thyroid cells, and glial cells.

How frequently do epithelial cells and bone marrow cells divide?

Frequently, with a division cycle of 12 to 24 hours.

What is the Hayflick limit?

The limit specifying that most normal somatic cells divide 20 to 50 times before dying.

How often do embryonic cells divide?

Every 20 minutes.

Which types of cells possess the ability to divide indefinitely?

Cancerous cells or immortalized cells in cell culture.

What internal signals influence cell division?

Kinases and phosphatases.

What external signals influence cell division?

Growth factors, direct cell contact, and extracellular surface interaction.

How do external growth factors initiate cell cycle control?

They bind to surface receptors and trigger intracellular signaling pathways.

How is the cell cycle defined?

A controlled sequence of events by which a cell duplicates its genome, doubles its content, and eventually divides into 2 identical daughter cells.

What are the two major functional divisions of the cell cycle?

Interphase (long, non-dividing phase) and Mitosis (short, dividing phase).

In cultured mammalian cells, what is the duration of the $G_1$ phase?

10 hours.

In cultured mammalian cells, what is the duration of the $S$ phase?

7.5 hours.

In cultured mammalian cells, what is the duration of the $G_2$ phase?

3.5 hours.

In cultured mammalian cells, what is the duration of the $M$ phase?

1.0 hour.

What is the total generation time for cultured mammalian cells as depicted in the cell-cycle diagram?

22 hours.

What is the primary function of interphase?

To prepare the cell for mitosis.

What metabolic events characterize the $G_1$ phase of interphase?

Cells are metabolically active and grow continuously, with active RNA and protein synthesis.

What major nuclear event takes place during the $S$ phase?

DNA replication, which causes the cell's DNA content to double.

What two preparations occur during the $G_2$ phase?

Protein synthesis in preparation for division and duplication of centrosomes.

What type of cell division occurs in somatic cells to generate identical daughter cells?

Mitosis (equatorial division).

What is karyokinesis?

The separation of chromosomes divided into 4 stages.

What is cytokinesis?

The division of the cell cytoplasm.

What changes occur to chromosomes and nuclear structures during prophase?

Duplicated chromosomes (sister chromatids) condense, while the nuclear envelope and nucleolus disintegrate.

What rearranges in the cytoskeleton during prophase?

The cytoskeletal network disassembles and microtubules assemble into the mitotic spindle.

Where do centrosomes migrate during prophase?

They move toward opposite poles of the cell.

How many centrioles are located inside each centrosome during prophase?

2 centrioles.

To what structure on chromosomes do spindle fibers attach during metaphase?

Kinetochores on the surface of centromeres.

What alignment structure forms at the equator of the spindle during metaphase?

The metaphase plate.

What is a kinetochore?

A disk-shaped structure consisting of more than 100 proteins on centromeres that allows attachment of spindle fibers.

How are spindle microtubules oriented with respect to their ends at poles and kinetochores?

Microtubules are anchored by their minus ($-$) ends to the poles and by their plus ($+$) ends to kinetochores.

In this diagram of kinetochore microtubules, which ends point toward the kinetochores?

The plus ($+$) ends.

What two events define the transition into anaphase?

Centromeres split to separate sister chromatids, and chromatids move to opposite poles.

What mechanism moves sister chromatids to opposite poles during anaphase?

The shortening of spindle fibers.

What structural reformations occur during telophase?

Nuclear envelopes assemble around chromosome clusters, and the nucleolus and organelles reform.

What contractile structure appears during telophase to prepare for cytoplasmic division?

The contractile ring.

Which microfilaments compose the cleavage furrow during cytokinesis?

Parallel sliding microfilaments of actin and myosin.

What is the midbody in cytokinesis?

A thin intercellular bridge formed as the cleavage furrow deepens before full separation into daughter cells.

What are cell cycle checkpoints?

Binary switches and surveillance mechanisms that monitor and regulate cell cycle progression.

What three sequential components make up a checkpoint pathway?

Event sensors, a signaling pathway, and an effector.

What action does an effector take in a checkpoint pathway?

It halts cell cycle progression and activates repair mechanisms.

What parameters are assessed at the $G_1$ checkpoint?

Cell size, nutrients/energy, molecular cues, and DNA integrity.

What happens if a cell receives a "STOP" signal at the $G_1$ checkpoint?

It exits the active cell cycle and moves into the $G_0$ state.

Why is the $G_1$ checkpoint termed the restriction point?

Because it is the most important, rate-limiting step determining whether a cell commits to division.

What defines a quiescent cell in $G_0$?

A non-dividing cell that can re-enter the cell cycle when receiving appropriate signals.

What defines a senescent cell in $G_0$?

An old cell that is permanently withdrawn from the cell cycle.

What defines a terminally differentiated cell in $G_0$?

A fully-functioning cell that is permanently withdrawn from the cell cycle.

What conditions are checked at the $G_2/M$ checkpoint?

That DNA replication is finalized and there is no DNA damage.

What conditions are checked at the $M$ (spindle) checkpoint?

Chromosome attachment to spindle microtubules and readiness of chromatids for separation.

What occurs if the $M$ checkpoint detects an uncorrectable problem and signals "STOP"?

Apoptosis.

What role do cyclins play in relation to cyclin-dependent kinases (Cdks)?

Cyclins serve as the catalytic/regulatory subunit of cyclin-dependent kinases.

What enzymatic activity do active Cyclin-Cdk complexes perform?

They phosphorylate and activate target proteins during checkpoint transitions.

Which Cyclin and Cdks respond to growth factors during early $G_1$ phase?

Cyclin D paired with Cdk4 or Cdk6.

Which Cyclin-Cdk complex regulates the transition from $G_1$ to $S$ phase?

Cyclin E - Cdk2.

Which Cyclin-Cdk complex drives DNA synthesis during the $S$ phase?

Cyclin A - Cdk2.

Which Cyclin pairs with Cdk1 to promote Mitosis?

Cyclin B.

What structural motif obscures the active site of an inactive Cdk?

The T-loop.

According to the Cdk activation scheme shown, what three states mark Cdk activation?

(A) Inactive Cdk, (B) Partly active Cdk (bound to cyclin), and (C) Fully active Cdk (phosphorylated by CAK).

What enzyme provides the activating phosphate for full Cdk activation?

Cdk-activating kinase (CAK).

How do CKI (cyclin kinase inhibitors) block enzymatic activity of Cdk complexes?

They bind to cyclins and Cdks, distorting the active site.

Why do cells in $G_0$ remain non-dividing?

They do not synthesize cyclins or CDKs, and the Rb-E2F complex inhibits progression.

In the $G_1$ signaling pathway shown, how do growth factors trigger E2F release?

Growth factors (mitogens) stimulate $G_1$-Cdks to phosphorylate Rb (retinoblastoma protein), causing it to release E2F.

What is the function of free E2F once released from Rb?

E2F stimulates transcription of $G_1/S$ phase-CDKs to promote passage through the $G_1$ checkpoint.

What is the S-phase promoting factor (SPF) and what is its action at origins of replication?

SPF is the $S$ phase-Cdk complex; it phosphorylates helicase and recruits helicase activators (Cdc45/Sld3, Dpb11/Sld2, GINS) to initiate replication.

How do Wee1 kinase and Cdc25 phosphatase oppositely regulate MPF (Mitosis Promoting Factor)?

Wee1 kinase inhibits MPF by phosphorylation ($Y^{15}$ and $T^{14}$), while Cdc25 phosphatase dephosphorylates MPF to activate it.

How does active MPF trigger exit from mitosis?

MPF activates APC/C, which marks mitotic cyclins for degradation by ubiquitination.

In this sister chromatid separation pathway, what enzyme complex ubiquitinates securin to liberate separase?

APC/C with Cdc20.

In the p53 DNA damage pathway shown, how does p53 halt cell cycle progression?

Damaged DNA activates ATM/ATR to stabilize p53, which produces p21 (a CKI) to inhibit Cdk2/Cyclin E and arrest the cell cycle.