Cell Cycle Phases and Regulation (2C) - Bio & Biochem

1. What is the primary function of p$53$ in cell-cycle regulation after DNA damage?

   Induces cell-cycle arrest or apoptosis via transcriptional control. p$53$ activates genes for cycle arrest or apoptosis to eliminate damaged cells and maintain genomic stability.

2. What is the immediate role of separase during the metaphase-to-anaphase transition?

   Cleaves cohesin to separate sister chromatids. Separase activation cleaves cohesin rings, enabling sister chromatid separation during anaphase.

3. What is the primary purpose of S phase in the cell cycle?

   DNA replication (genome duplication). S phase duplicates the genome to provide identical DNA copies for distribution to daughter cells during division.

4. What is the immediate effect of retinoblastoma protein (Rb) when it is hypophosphorylated?

   It inhibits E$2$F and blocks entry into S phase. Hypophosphorylated Rb represses E$2$F to prevent transcription of genes needed for S phase entry.

5. Which checkpoint primarily verifies completion of DNA replication and DNA integrity before mitosis?

   G$2$/M checkpoint. The G$2$/M checkpoint confirms complete and accurate DNA replication to avoid errors in chromosome segregation.

6. What is the function of ATM/ATR kinases in response to DNA damage or replication stress?

   Activate checkpoint signaling (for example, via Chk$1$/Chk$2$). ATM/ATR detect damage and phosphorylate effectors like Chk$1$/Chk$2$ to activate checkpoints and arrest the cycle.

7. What is the primary purpose of G$1$ phase in the cell cycle?

   Cell growth and preparation for DNA synthesis. G$1$ phase enables cellular growth and synthesis of proteins and organelles necessary before committing to DNA replication.

8. How do cyclin levels typically change across the cell cycle compared with CDK levels?

   Cyclins oscillate; CDK protein levels are relatively constant. Cyclin levels fluctuate to temporally control CDK activity, while CDKs remain stable throughout the cycle.

9. What is the effect of Rb phosphorylation by G$1$ cyclin-CDK complexes?

   Rb releases E$2$F, promoting transcription of S-phase genes. Phosphorylation inactivates Rb, allowing E$2$F to drive expression of DNA synthesis genes.

10. What is the core biochemical function of cyclin-dependent kinases (CDKs)?

    Serine/threonine kinases that phosphorylate cell-cycle targets. CDKs phosphorylate substrates to regulate transitions between cell cycle phases.

11. Which checkpoint ensures all chromosomes are properly attached to the spindle before anaphase?

    Spindle assembly checkpoint (metaphase checkpoint). The spindle assembly checkpoint halts mitosis until all chromosomes achieve bipolar spindle attachment for equal segregation.

12. What is the role of E$2$F transcription factors in the cell cycle?

    Activate transcription of genes required for S phase. E$2$F factors transcribe genes essential for DNA replication and S phase progression.

13. What is the defining chromosomal event of S phase that changes DNA content but not chromosome number?

    Sister chromatid formation (DNA content doubles). DNA replication in S phase forms sister chromatids, doubling DNA without altering chromosome count.

14. Which two key substrates are ubiquitinated to allow anaphase onset and mitotic exit?

    Securin and cyclin B. Ubiquitination of securin activates separase, while cyclin B degradation inactivates CDK$1$ for mitotic exit.

15. Identify the cell-cycle phase when chromosomes are most condensed and best visualized on a karyotype.

    Metaphase of mitosis. Chromosomes condense maximally in metaphase to facilitate alignment and visualization on the mitotic spindle.

16. Which checkpoint is called the restriction point, and what decision does it control?

    G$1$/S checkpoint; commit to division or enter G$0$. The restriction point at G$1$/S evaluates signals to decide on cell division commitment or quiescence.

17. What is G$0$ phase, and when do cells typically enter it?

    Quiescent nondividing state entered from G$1$. G$0$ represents a resting state where cells exit the cycle from G$1$ to perform specialized functions without dividing.

18. What is the role of the anaphase-promoting complex/cyclosome (APC/C) in M phase?

    E$3$ ubiquitin ligase that triggers anaphase and mitotic exit. APC/C ubiquitinates targets to promote their degradation, enabling anaphase and mitotic progression.

19. Identify the direct consequence of loss-of-function in p$53$ for cell-cycle control.

    Failure of DNA-damage arrest; increased survival of damaged cells. p$53$ loss impairs damage response, allowing proliferation of mutated cells and promoting tumorigenesis.

20. Which CDK inhibitor is transcriptionally upregulated by p$53$ to enforce G$1$/S arrest?

    p$21$. p$53$ induces p$21$ to inhibit CDKs, halting progression at G$1$/S in response to damage.

21. What must bind to a CDK to activate it for cell-cycle progression?

    A cyclin. Cyclin binding confers activity and specificity to CDKs for phase-specific phosphorylation events.

22. What are the four main phases of the eukaryotic cell cycle in order?

    G$1$ S G$2$ M. The eukaryotic cell cycle progresses sequentially through these phases to coordinate growth, DNA replication, and division, ensuring genetic fidelity.

23. Which option best describes how growth factors promote G$1$ to S progression?

    Increase cyclin expression to activate CDKs and phosphorylate Rb. Growth factors upregulate cyclins via signaling pathways, activating CDKs to phosphorylate Rb and release E$2$F for S phase genes.

24. What is the primary purpose of G$2$ phase in the cell cycle?

    Growth and preparation for mitosis; DNA damage check. G$2$ phase allows further cellular growth and checks for DNA replication errors to prevent mitotic defects.

25. What is the primary purpose of M phase in the cell cycle?

    Mitosis and cytokinesis to form two daughter cells. M phase divides the nucleus and cytoplasm to produce genetically identical daughter cells.

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