Quality control of DNA break metabolism: in the 'end', it's a good thing

Roland Kanaar, C.L. Wyman, R Rothstein

Research output: Contribution to journalArticleAcademicpeer-review

50 Citations (Scopus)

Abstract

DNA ends pose specific problems in the control of genetic information quality. Ends of broken DNA need to be rejoined to avoid genome rearrangements, whereas natural DNA ends of linear chromosomes, telomeres, need to be stable and hidden from the DNA damage response. Efficient DNA end metabolism, either at induced DNA breaks or telomeres, does not result from the machine-like precision of molecular reactions, but rather from messier, more stochastic processes. The necessary molecular interactions are dynamically unstable, with constructive and destructive processes occurring in competition. In the end, quality control comes from the constant building up and tearing down of inappropriate, but also appropriate reaction steps in combination with factors that only slightly shift the equilibrium to eventually favour appropriate events. Thus, paradoxically, enzymes antagonizing DNA end metabolism help to ensure that genome maintenance becomes a robust process.
Original languageUndefined/Unknown
Pages (from-to)581-588
Number of pages8
JournalEMBO Journal
Volume27
Issue number4
DOIs
Publication statusPublished - 2008

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