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DNA damage sensing

Friday 3 March 2006

DNA damage sensing

To function properly, cell-cycle checkpoints require sensors of DNA damage, signal transducers, and effector molecules. The sensors and transducers of DNA damage appear to be similar for the G1/S and G2/M checkpoints.

They include, as sensors, proteins of the RAD family and ataxia telangiectasia mutated (ATM) and as transducers, the CHK kinase families. The checkpoint effector molecules differ, depending on the cell-cycle stage at which they act.

In the G1/S checkpoint, cell-cycle arrest is mostly mediated through p53, which induces the cell-cycle inhibitor p21. Arrest of the cell cycle by the G2/M checkpoint involves both p53-dependent and independent mechanisms.

Defect in cell-cycle checkpoint components is a major cause of genetic instability in cancer cells.

References

- Zou, L.; Elledge, S. J. : Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300: 1542-1548, 2003. PubMed ID : 12791985

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