Regulating DNA Repair

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Science  04 Apr 2014:
Vol. 344, Issue 6179, pp. 11
DOI: 10.1126/science.344.6179.11-c

Chromosomes carry the intricate code that makes and organizes cells and organisms. But chromosomes can break, causing a serious potential threat to cell and organismal survival. Repairing such breaks is vital, but repair can come with its own dangers, as certain repair pathways are necessarily error-prone—restoring chromosome integrity at the cost of introducing mutations into the genome. Microhomology-mediated end joining (MMEJ) is an error-prone form of repair that relies on very small (∼5 to 25 base pairs) fortuitous homologies near the broken ends of chromosomes, which allow them to come together and be rejoined. A microhomology signature is often seen in breakpoints in chromosome arrangements in cancers and other diseases, suggesting that MMEJ is commonly involved in such genome derangement. Deng et al. investigated MMEJ in the budding yeast Saccharomyces cerevisiae. They find that although resection [the trimming back of one of the DNA stands to generate a single-stranded DNA (ssDNA) tail] at the ends of the breaks is important to expose regions of microhomology internal to the break, it is not rate-limiting for repair. On the other hand, replication protein A, which binds ssDNA, actively prevents spontaneous annealing between the microhomologies and suppresses MMEJ.

Nat. Struct. Mol. Biol. 10.1038/nsmb.2786 (2014).

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