Checkpoints in the Cell Cycle


Surveillance mechanisms stop progression through the cell cycle at specific checkpoints (at the G1 → S, G2 → M and metaphase → anaphase transitions) if certain crucial requirements have not been met. These checkpoint controls are essential for maintaining genomic integrity and balanced growth and division.

Keywords: G1 checkpoint; G2 checkpoint; spindle checkpoint; restriction point; Start

Figure 1.

Accelerators (green) and brakes (red) of the cell cycle engine. Checkpoint pathways (dashed lines) modulate the activities of the accelerators and brakes. Pro, prophase; Meta, metaphase; Ana, anaphase; Telo, telophase; CKI, cyclin kinase inhibitor; DNA, deoxyribonucleic acid; Rb, retinoblastoma protein; Sk, starter kinase.

Figure 2.

Three different ways to regulate cyclin‐dependent kinase (Cdk) activity. Continuous arrows represent chemical transformations, while dashed arrows indicate regulatory signals (arrowhead indicates activation, blunt end indicates inhibition, diamond head indicates both activatory and inhibitory effects). APC, anaphase‐promoting complex; CKI, cyclin dependent kinase inhibitor; SCF, Skp1–Cullin–Fbox protein complex; Ub, ubiquitin.

Figure 3.

Mammalian checkpoint pathways that block cell cycle progression as a consequence of blocked deoxyribonucleic acid (DNA) replication and DNA damage. CIP, Cdk‐interacting protein.

Figure 4.

Checkpoint pathways that block mitotic transitions as a consequence of spindle damage. APC, anaphase‐promoting complex.



Bartek J and Lukas J (2001) Pathways governing G1/S transition and their response to DNA damage. FEBS Letters 490: 117–122.

Hartwell LH and Weinert TA (1989) Checkpoints: controls that ensure the order of cell cycle events. Science 246: 629–634.

Hartwell LH, Culotti J, Pringle JR and Reid BJ (1974) Genetic control of the cell division cycle in yeast. Science 183: 46–51.

Hoyt MA, Totis L and Roberts BT (1991) S. cerevisiae genes required for cell cycle arrest in response to loss of microtubule function. Cell 66: 507–517.

Lengauer C, Kinzler KW and Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396: 643–649.

Li R and Murray AW (1991) Feedback control of mitosis in budding yeast. Cell 66: 519–531.

Nurse P (1975) Genetic control of cell size at cell division in yeast. Nature 256: 547–551.

Pardee AB (1974) A restriction point for control of normal animal cell proliferation. Proceedings of the National Academy of Sciences of the USA 71: 1286–1290.

Walworth NC (2000) Cell‐cycle checkpoint kinases: checking in on the cell cycle. Current Opinion in Cell Biology 12: 697–704.

Zetterberg A and Larsson O (1985) Kinetic analysis of regulatory events in G1 leading to proliferation or quiescence of Swiss 3T3 cells. Proceedings of the National Academy of Sciences of the USA 82: 5365–5369.

Further Reading

Canman CE (2001) Replication checkpoint: preventing mitotic catastrophe. Current Biology 11: R121–124.

Cerutti L and Simanis V (2000) Controlling the end of the cell cycle. Current Opinion in Genetics and Development 10: 65–69.

Gardner RD and Burke DJ (2000) The spindle checkpoint: two transitions, two pathways. Trends in Cell Biology 10: 154–158.

Nurse P (1997) Checkpoint pathways come of age. Cell 91: 865–867.

O'Connell MJ, Walworth NC and Carr AM (2000) The G2‐phase DNA‐damage checkpoint. Trends in Cell Biology 10: 296–303.

Rhind N and Russell P (2000) Chk1 and Cds1: linchpins of the DNA damage and replication checkpoint pathways. Journal of Cell Science 113: 3889–3896.

Shah JV and Cleveland DW (2000) Waiting for anaphase: Mad2 and the spindle assembly checkpoint. Cell 103: 997–1000.

Zhou BB and Elledge SJ (2000) The DNA damage response: putting checkpoints in perspective. Nature 408: 433–439.

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How to Cite close
Novák, Béla, Sible, Jill C, and Tyson, John J(Feb 2003) Checkpoints in the Cell Cycle. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0001355]