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

Authors: Daley, James M; Jimenez-Sainz, Judit; Wang, Weibin; Miller, Adam S; Xue, Xiaoyu; Nguyen, Kevin A; Jensen, Ryan B; Sung, Patrick

Published In Cell Rep, (2017 Oct 10)

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.

PubMed ID: 29020620 Exiting the NIEHS site

MeSH Terms: Animals; Carrier Proteins/genetics; Carrier Proteins/metabolism*; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism*; DNA Helicases/genetics; DNA Helicases/metabolism; Endodeoxyribonucleases/genetics; Endodeoxyribonucleases/metabolism; HEK293 Cells; Humans; MRE11 Homologue Protein/genetics; MRE11 Homologue Protein/metabolism; Mice; Multifunctional Enzymes/genetics; Multifunctional Enzymes/metabolism; Protein Binding; Protein Multimerization; RecQ Helicases/genetics; RecQ Helicases/metabolism; Recombinational DNA Repair*; Sf9 Cells; Spodoptera; Up-Regulation

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