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Crit Rev Biochem Mol Biol. 2016 May-Jun;51(3):195-212. doi: 10.3109/10409238.2016.1172552. Epub 2016 Apr 20.

Mechanism and regulation of DNA end resection in eukaryotes.

Author information

1
a Department of Microbiology & Immunology , Columbia University Medical Center , New York , USA.

Abstract

The repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) is initiated by nucleolytic degradation of the 5'-terminated strands in a process termed end resection. End resection generates 3'-single-stranded DNA tails, substrates for Rad51 to catalyze homologous pairing and DNA strand exchange, and for activation of the DNA damage checkpoint. The commonly accepted view is that end resection occurs by a two-step mechanism. In the first step, Sae2/CtIP activates the Mre11-Rad50-Xrs2/Nbs1 (MRX/N) complex to endonucleolytically cleave the 5'-terminated DNA strands close to break ends, and in the second step Exo1 and/or Dna2 nucleases extend the resected tracts to produce long 3'-ssDNA-tailed intermediates. Initiation of resection commits a cell to repair a DSB by HR because long ssDNA overhangs are poor substrates for non-homologous end joining (NHEJ). Thus, the initiation of end resection has emerged as a critical control point for repair pathway choice. Here, I review recent studies on the mechanism of end resection and how this process is regulated to ensure the most appropriate repair outcome.

KEYWORDS:

DNA repair; Dna2; Exo1; Mre11; Sae2/CtIP; double-strand break; end joining; recombination

PMID:
27098756
PMCID:
PMC4957645
DOI:
10.3109/10409238.2016.1172552
[Indexed for MEDLINE]
Free PMC Article

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