Cell Cycle Regulation Simple notes
Cell cycle checkpoints are critical regulatory points in the cell cycle that ensure the proper progression of cell division through different phases. Cell cycle checkpoints are mechanisms that monitor the progression of the cell cycle and prevent the division of damaged or incomplete cells.
Watch our video here Cell Cycle Regulation and Checkpoints|| G1, G2 and M Checkpoint Regulation in 9 minutes
- DNA integrity
- Proper chromosome alignment
- Adequate cell size and nutrient availability
Key Checkpoints:
- G1 checkpoint
- G2 checkpoint
- M checkpoint (spindle
assembly checkpoint)
Regulation by CDKs, Cyclins, and Other
Proteins
- Cyclins:
- Regulatory proteins that activate CDKs at specific phases.
- Levels fluctuate throughout the cell cycle, ensuring timely
activation.
- CDKs (Cyclin-dependent Kinases):
- Enzymes that, when activated by cyclins, phosphorylate target
proteins to drive cell cycle progression.
- Tumor Suppressor Proteins (e.g., p53, Rb):
- Monitor DNA damage and cellular stress; can halt the cell
cycle for repair or induce apoptosis.
- Kinases (ATM/ATR):
- Detect DNA damage and activate checkpoints to prevent
progression until issues are resolved.
G1 Checkpoint (Restriction Point)
- Location: At the end of G1 phase,
before entering S phase.
- Major Events:
- Checks for DNA damage.
- Assesses cell size and nutrient availability.
- Determines if growth signals (mitogens) are present.
G1 Checkpoint (Restriction Point)
Role of Cyclins:
Cyclin D: Binds to CDK4 and CDK6, forming a
cyclin-CDK complex that is essential for the transition from G1 to S phase.
Role of CDKs:
CDK4/6: Once activated by Cyclin D, these
CDKs phosphorylate the retinoblastoma protein (Rb). This phosphorylation leads
to the release of E2F transcription factors, which promote the expression of
genes necessary for DNA synthesis and progression into S phase.
Regulatory Proteins:
p53: If DNA damage is detected, p53 levels
increase, leading to the transcription of p21, a CDK inhibitor that halts the
cell cycle at this checkpoint.
G2 Checkpoint
Location: At the end of G2 phase, before
entering M phase.
Major Events:
·
Checks for DNA replication
completeness.
·
Assesses DNA damage repair.
G2 Checkpoint
Role of Cyclins:
Cyclin B: Accumulates during G2 and binds
to CDK1, forming the cyclin B-CDK1 complex.
Role of CDKs:
CDK1: Once activated by Cyclin B, it
phosphorylates multiple substrates required for mitosis. This complex is
essential for transitioning from G2 to M phase.
Regulatory Proteins:
ATM/ATR Kinases: These proteins sense DNA
damage and activate checkpoint kinases (e.g., Chk1 and Chk2) that can inhibit
CDK1 activity, preventing entry into mitosis until DNA repair is complete.
M Checkpoint (Spindle Assembly
Checkpoint)
Location:
During metaphase of mitosis.
Major Events:
- Ensures all chromosomes are properly attached to the spindle
apparatus.
- Prevents anaphase from occurring until all chromosomes are
aligned.
M Checkpoint (Spindle Assembly Checkpoint)
Role of Cyclins:
Cyclin B: Continues to be active during
mitosis, maintaining its association with CDK1.
Role of CDKs:
CDK1: This complex ensures that all
components required for mitosis are in place. It phosphorylates proteins
necessary for chromosome condensation and spindle formation.
Regulatory Proteins:
Mad2 and BubR1: These proteins monitor
spindle attachment. If any chromosomes are not properly aligned on the
metaphase plate, they inhibit the anaphase-promoting complex (APC), preventing
the degradation of Cyclin B. This inhibition keeps CDK1 active until all
chromosomes are correctly attached, ensuring proper segregation during
anaphase.
Conclusion
In summary, cyclins and CDKs are essential
for cell cycle regulation at each checkpoint:
- G1 Checkpoint: Cyclin D/CDK4/6
promotes progression to S phase; p53 can halt this process if DNA damage
is detected.
- G2 Checkpoint: Cyclin B/CDK1 drives
entry into mitosis; ATM/ATR kinases prevent progression if DNA is damaged.
- M Checkpoint: Cyclin B/CDK1 ensures
proper chromosome alignment; Mad2 and BubR1 inhibit progression until all
chromosomes are correctly attached.