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Nucleic Acids Res May 1, 2012; 40 (10): 4496-506.

Analysis of MRE11''s function in the 5''-->3'' processing of DNA double-strand breaks.

Liao S , Guay C , Toczylowski T , Yan H .

The resection of DNA double-strand breaks (DSBs) into 3'' single-strand tails is the initiating step of homology-dependent repair pathways. A key player in this process is the MRE11-RAD50-NBS1 complex, but its contribution to and mechanistic role in resection are not well understood. In this study, we took advantage of the Xenopus egg extract system to address these questions. We found that depletion of MRE11 caused a dramatic inhibition of 5''-resection, even for the first nucleotide at the 5''-end. Depletion of Xenopus CtIP also inhibited 5''-strand resection, but this inhibition could be alleviated by excess MRN. Both MRE11 and CtIP could be bypassed by a DNA that carried a 3''-ss-tail. Finally, using purified proteins, we found that MRN could stimulate both the WRN-DNA2-RPA pathway and the EXO1 pathway of resection. These findings provide important insights into the function of MRE11 in 5''-strand resection.

PubMed ID: 22319209
PMC ID: PMC3378884
Article link: Nucleic Acids Res
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: ddc dna2 exo1 mre11 nbn rad50 rbbp8 rpa1 wrn
Antibodies: Mre11a Ab1

Article Images: [+] show captions
References [+] :
Bernstein, The RecQ DNA helicases in DNA repair. 2010, Pubmed