Cell Cycle and Cell Cycle Regulation COMPILED BY: Bhuvanesh S.K. III Sem M.Sc. Microbiology Dayananda Sagar College of Biological Sciences, Bangalore
Acknowledgements Dr. P S Roa Mrs. Shobha K Jayana Divya mam (Guide)
Hithishi mam Sushma mam Dr. John B Mamata B mam Mamata TM mam
OUTLINE 1. Phases of the cell cycle – 1.1 M phase – 1.2 Interphase • 1.2.1 G1 phase • 1.2.2 S phase • 1.2.3 G2 phase – 1.3 G0 phase 2. Regulation of cell cycle – 2.1 Role of Cyclins and CDKs • 2.1.1 General mechanism of cyclin-CDK interaction • 2.1.2 Specific action of cyclin-CDK complexes – 2.2 Cell cycle inhibitors 3. Checkpoints 4 Conclusion 5 References
Phases of the Cell Cycle INTERPHASE (90%) (the cell continuously grows) • G1 phase: gap between M and S phases • S phase: DNA replication • G2 phase: gap between S and M phases
• •
M PHASE (10%) Mitosis: nuclear division Cytokinesis: cytoplamatic division
MITOSIS
Cytokinesis
Real Pictures
Prophase
Metaphase
Anaphase
Telophase
Picture adopted from: http://www.micro.utexas.edu/courses/levin/bio304/genetics/celldiv.html
Real Pictures
Anaphase
Interphase
Prophase Telophase
Metaphase Picture adopted from: http://www.uoguelph.ca/zoology/devobio/210labs/mitosis1.html
Real Pictures
Late Prophase I Metaphase I
Prophase II
Metaphase II
Anaphase I
Anaphase II
Telophase I
Telophase II
Interphase II
Cytokinesis
The comparison of meiosis and mitosis
Cell cycle proteins 1) Cyclins. Activator proteins that are up- or downregulated depending on the phase of the cell cycle. • Cyclin-dependent kinases (CDKs). Serine/threonine kinases that require the binding of a cyclin (or related protein) for full activity. Their range of substrates is not fully defined, but interfering with their activity arrests or slows the cycle. • Cyclin-dependent kinase inhibitors (CKIs). Small peptides that block cyclin/CDK activity either by forming an inactive complex or by acting as a competitive CDK ligand. • DNA replication proteins. DNA polymerases and associated proteins such as proliferating cell nuclear antigen (PCNA) and mini-chromosome maintenance (MCM) proteins, as well as proteins that assure that each origin of replication initiates replication only once per cycle. These include origin recognition complex (ORC) proteins, CDT1 and its suppressor, geminin. • Checkpoint proteins. Members of a network of proteins that monitor DNA integrity and arrest the cell cycle until DNA damage can be repaired.
Leland H. Hartwell
R. Timothy (Tim) Hunt
Sir Paul M. Nurse
The Nobel Prize in Physiology or Medicine 2001 "for their discoveries of key regulators of the cell cycle"
CYCLIN/CDK tyr15-P thr14-P
Regulated by: -tyr15 phosphorylation • inhibitory kinases • activating phosphatases -direct interaction • inhibitor- Wee1 •Activator-Cdc25
P-thr161
cdk1 (cdc2)
cyclin B
(a) Free CDK2 (b) Low-activity cyclin A−CDK2 (c) High-activity cyclin A−CDK2
Regulating a CDK
Regulation 1960 Process Description
1995 Process Description
CONCLUSION • Cancer • Drug target
DISCUSSION ?
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