Quality control of DNA break metabolism: In the 'end', it's a good thing
EMBO Journal , Volume 27 - Issue 4 p. 581- 588
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.
|DNA double-strand breaks, Homologous recombination, Non-homologous DNA end-joining, Telomeres|
|Free full text at PubMed|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Kanaar, R, Wyman, C, & Rothstein, R. (2008). Quality control of DNA break metabolism: In the 'end', it's a good thing. EMBO Journal, 27(4), 581–588. doi:10.1038/emboj.2008.11