Q.72 In normal cells, progress through the cell cycle is tightly regulated and each step must be completed before the next step can begin.

There are at least three distinct points in the cell cycle at which the cell monitors external signals and internal equilibrium before proceeding to the next stage. These are the G1/S, the G2/M and M checkpoints.

In addition to regulating the cell cycle at the checkpoints, the cell controls progress through the cell cycle by means of two classes of proteins: cyclins and cyclin-dependent kinases (CDKs).

Based on the above context, answer the following questions:

1. Cyclin D2 accumulates during early G1 phase
2. Cyclin E appears during S phase
3. Cyclin B peaks during M phase
4. Cyclin A appears during late G1 phase

   Cyclin B peaks during M phase.

   Cyclin B forms the mitosis-promoting factor (MPF) complex with CDK1, peaking at metaphase to drive chromosome condensation, nuclear envelope breakdown, and spindle assembly before APC/C-mediated degradation triggers anaphase.

   Option Analysis

   Cyclin D2 accumulates during early G1 phase
   Cyclin D family (D1, D2, D3) accumulates throughout G1 in response to mitogens, binding CDK4/6 to initiate Rb phosphorylation. Tissue-specific expression (D2 prominent in B-cells), but continuous G1 rise, not “early” peak. Partially correct but imprecise.​

   Cyclin E appears during S phase
   Cyclin E synthesized late G1, peaks at G1/S transition, activates CDK2 for DNA replication initiation (pre-RC loading). Degraded by SCF-Fbxw7 during S phase progression. Precedes S phase entry. Incorrect.

   Cyclin B peaks during M phase
   Mitotic cyclin B1 synthesized G2, accumulates progressively, nuclear translocation late G2. Peaks metaphase via CDK1 autoamplification. APC/C-Cdc20 ubiquitinates cyclin B post-SAC satisfaction, enabling mitotic exit. Correct.

   Cyclin A appears during late G1 phase
   Cyclin A transcription begins late G1 via E2F, but protein levels rise S phase (CDK2 partner for replication fork progression), persists G2 (CDK1 partner), degraded prior to cyclin B peak. Not late G1 appearance. Incorrect.​

   Cyclin B peaks during M phase coordinates mitotic entry via 30+ downstream targets including condensins, lamins, APC/C inhibitors, ensuring irreversible commitment to division.

   Cyclin Oscillation Patterns

   Cyclin	Phase	CDK Partner	Key Substrates	Degradation Trigger
   D1/D2/D3	G1	CDK4/6	Rb (partial)	SCF-Skp2 (G1/S)
   E	G1/S	CDK2	Rb (complete), NPAT, Cdc6	SCF-Fbxw7 (S)
   B1	G2/M	CDK1	Lamins, CyclinB, APC/C	APC/C-Cdc20 (metaphase)
   A2	S/G2	CDK2/1	E2F1, Cdc6	APC/C-Cdh1 (early M)

   MPF Activation Cascade

   1. Cyclin B nuclear import (phospho-Cdk1 export block lifted)

   2. Cdk1 T14/Y15 dephosphorylation (Cdc25B/C activation)

   3. Positive feedback: MPF → Cdc25 ↑ → Cdk1 ↑ → MPF ↑

   4. Peak metaphase: [CyclinB-Cdk1] drives all mitotic events

   5. Sudden drop: SAC satisfaction → Cdc20 activation → Ubiquitinylation → Anaphase

   Checkpoint Integration

   G2/M: DNA damage → Chk1 → Wee1 ↑ → Cdk1 inhibitory phosphorylation blocks cyclin B-Cdk1. Mitotic exit requires cyclin B destruction; overexpression causes mitotic arrest. Cancer mutations (CCNB1 amplification, CDC25B overexpression) drive genomic instability.​