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- Title
Bidirectional resection of DNA double-strand breaks by Mre11 and Exo1.
- Authors
Garcia, Valerie; Phelps, Sarah E. L.; Gray, Stephen; Neale, Matthew J.
- Abstract
Repair of DNA double-strand breaks (DSBs) by homologous recombination requires resection of 5?-termini to generate 3?-single-strand DNA tails. Key components of this reaction are exonuclease 1 and the bifunctional endo/exonuclease, Mre11 (refs 2-4). Mre11 endonuclease activity is critical when DSB termini are blocked by bound protein-such as by the DNA end-joining complex, topoisomerases or the meiotic transesterase Spo11 (refs 7-13)-but a specific function for the Mre11 3?-5? exonuclease activity has remained elusive. Here we use Saccharomyces cerevisiae to reveal a role for the Mre11 exonuclease during the resection of Spo11-linked 5?-DNA termini in vivo. We show that the residual resection observed in Exo1-mutant cells is dependent on Mre11, and that both exonuclease activities are required for efficient DSB repair. Previous work has indicated that resection traverses unidirectionally. Using a combination of physical assays for 5?-end processing, our results indicate an alternative mechanism involving bidirectional resection. First, Mre11 nicks the strand to be resected up to 300 nucleotides from the 5?-terminus of the DSB-much further away than previously assumed. Second, this nick enables resection in a bidirectional manner, using Exo1 in the 5?-3? direction away from the DSB, and Mre11 in the 3?-5? direction towards the DSB end. Mre11 exonuclease activity also confers resistance to DNA damage in cycling cells, suggesting that Mre11-catalysed resection may be a general feature of various DNA repair pathways.
- Subjects
DNA repair; GENETIC recombination; EXONUCLEASES; DNA topoisomerases; SURGICAL excision
- Publication
Nature, 2011, Vol 479, Issue 7372, p241
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature10515