Sci. STKE, 28 November 2000
Cell Cycle Damage Report
The DNA damage checkpoint was originally described as a regulatory mechanism that was dispensable in the absence of damage, but caused arrest of the cell cycle once DNA damage was detected. In a review, Zhou and Elledge provide a more expansive view of the cellular response to DNA damage and suggest that the "checkpoint" itself is best understood as part of a larger process (which they term the "DNA damage response") that influences not only control of cell-cycle progression, but also of DNA repair mechanisms, telomere length, apoptosis, and other processes. They discuss proposed sensors of DNA damage, which include BASC (the BRCA1-associated genome surveillance complex), a large complex that comprises the breast cancer-associated tumor suppressor gene product BRCA1, the ataxia telangiectasia gene product ATM, and the Nijmegen breakage syndrome protein (Nbs1). A summary of the better-understood transducers and effectors of the damage response is followed by a look at some of the fascinating questions that remain to be resolved. For example, it is not enough to sense DNA damage. The cell also must sense the completion of the repair process. We have a sense of how E. coli manages this, but in mammalian systems, the primary subject of this review, a solution has yet to be described.
Zhou, B.-B.S., and Elledge, S.J. (2000) The DNA damage response: Putting checkpoints in perspective. Nature 408: 433-439. [Online Journal]
Citation: Damage Report. Sci. STKE 2000, tw1 (2000).
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