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DNA Repair (Amst). 2009 Sep 2;8(9):983-95. doi: 10.1016/j.dnarep.2009.04.017. Epub 2009 May 26.

DNA end resection: many nucleases make light work.

Author information

1
Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, United States.

Abstract

Double-strand breaks (DSBs) are deleterious DNA lesions and if left unrepaired result in severe genomic instability. Cells use two main pathways to repair DSBs: homologous recombination (HR) or non-homologous end joining (NHEJ) depending on the phase of the cell cycle and the nature of the DSB ends. A key step where pathway choice is exerted is in the 'licensing' of 5'-3' resection of the ends to produce recombinogenic 3' single-stranded tails. These tails are substrate for binding by Rad51 to initiate pairing and strand invasion with homologous duplex DNA. Moreover, the single-stranded DNA generated after end processing is important to activate the DNA damage response. The mechanism of end processing is the focus of this review and we will describe recent findings that shed light on this important initiating step for HR. The conserved MRX/MRN complex appears to be a major regulator of DNA end processing. Sae2/CtIP functions with the MRX complex, either to activate the Mre11 nuclease or via the intrinsic endonuclease, in an initial step to trim the DSB ends. In a second step, redundant systems remove long tracts of DNA to reveal extensive 3' single-stranded tails. One system is dependent on the helicase Sgs1 and the nuclease Dna2, and the other on the 5'-3' exonuclease Exo1.

PMID:
19473888
PMCID:
PMC2760233
DOI:
10.1016/j.dnarep.2009.04.017
[Indexed for MEDLINE]
Free PMC Article

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