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DNA Repair (Amst). 2015 Aug;32:66-74. doi: 10.1016/j.dnarep.2015.04.015. Epub 2015 May 1.

Biochemical mechanism of DSB end resection and its regulation.

Author information

1
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: james.daley@yale.edu.
2
Molecular and Cellular Biochemistry Department, Indiana University, Bloomington, IN 47405, USA.
3
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.

Abstract

DNA double-strand breaks (DSBs) in cells can undergo nucleolytic degradation to generate long 3' single-stranded DNA tails. This process is termed DNA end resection, and its occurrence effectively commits to break repair via homologous recombination, which entails the acquisition of genetic information from an intact, homologous donor DNA sequence. Recent advances, prompted by the identification of the nucleases that catalyze resection, have revealed intricate layers of functional redundancy, interconnectedness, and regulation. Here, we review the current state of the field with an emphasis on the major questions that remain to be answered. Topics addressed will include how resection initiates via the introduction of an endonucleolytic incision close to the break end, the molecular mechanism of the conserved MRE11 complex in conjunction with Sae2/CtIP within such a model, the role of BRCA1 and 53BP1 in regulating resection initiation in mammalian cells, the influence of chromatin in the resection process, and potential roles of novel factors.

KEYWORDS:

Double-strand breaks; Helicases; Nucleases; Recombination; Resection

PMID:
25956866
PMCID:
PMC4522330
DOI:
10.1016/j.dnarep.2015.04.015
[Indexed for MEDLINE]
Free PMC Article

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