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Cell Rep. 2017 Oct 10;21(2):324-332. doi: 10.1016/j.celrep.2017.09.048.

Enhancement of BLM-DNA2-Mediated Long-Range DNA End Resection by CtIP.

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
Department of Therapeutic Radiobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
3
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
4
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: patrick.sung@yale.edu.

Abstract

DNA double-strand break repair by homologous recombination entails the resection of DNA ends to reveal ssDNA tails, which are used to invade a homologous DNA template. CtIP and its yeast ortholog Sae2 regulate the nuclease activity of MRE11 in the initial stage of resection. Deletion of CtIP in the mouse or SAE2 in yeast engenders a more severe phenotype than MRE11 nuclease inactivation, indicative of a broader role of CtIP/Sae2. Here, we provide biochemical evidence that CtIP promotes long-range resection via the BLM-DNA2 pathway. Specifically, CtIP interacts with BLM and enhances its helicase activity, and it enhances DNA cleavage by DNA2. Thus, CtIP influences multiple aspects of end resection beyond MRE11 regulation.

KEYWORDS:

BLM; Bloom syndrome; CtIP; DNA2; double-strand break repair; end resection; homologous recombination

PMID:
29020620
PMCID:
PMC5689478
DOI:
10.1016/j.celrep.2017.09.048
[Indexed for MEDLINE]
Free PMC Article

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