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Catalytic and Noncatalytic Roles of the CtIP Endonuclease in Double-Strand Break End Resection.

Makharashvili, Nodar ; Tubbs, Anthony T. ; Yang, Soo-Hyun ; Wang, Hailong ; Barton, Olivia ; Zhou, Yi ; Deshpande, Rajashree A. ; Lee, Ji-Hoon ; Löbrich, Markus ; Sleckman, Barry P. ; Wu, Xiaohua ; Paull, Tanya T. (2014)
Catalytic and Noncatalytic Roles of the CtIP Endonuclease in Double-Strand Break End Resection.
In: Molecular cell, 54 (6)
Article, Bibliographie

Abstract

The carboxy-terminal binding protein (CtBP)-interacting protein (CtIP) is known to function in 5' strand resection during homologous recombination, similar to the budding yeast Sae2 protein, but its role in this process is unclear. Here, we characterize recombinant human CtIP and find that it exhibits 5' flap endonuclease activity on branched DNA structures, independent of the MRN complex. Phosphorylation of CtIP at known damage-dependent sites and other sites is essential for its catalytic activity, although the S327 and T847 phosphorylation sites are dispensable. A catalytic mutant of CtIP that is deficient in endonuclease activity exhibits wild-type levels of homologous recombination at restriction enzyme-generated breaks but is deficient in processing topoisomerase adducts and radiation-induced breaks in human cells, suggesting that the nuclease activity of CtIP is specifically required for the removal of DNA adducts at sites of DNA breaks.

Item Type: Article
Erschienen: 2014
Creators: Makharashvili, Nodar ; Tubbs, Anthony T. ; Yang, Soo-Hyun ; Wang, Hailong ; Barton, Olivia ; Zhou, Yi ; Deshpande, Rajashree A. ; Lee, Ji-Hoon ; Löbrich, Markus ; Sleckman, Barry P. ; Wu, Xiaohua ; Paull, Tanya T.
Type of entry: Bibliographie
Title: Catalytic and Noncatalytic Roles of the CtIP Endonuclease in Double-Strand Break End Resection.
Language: English
Date: 2014
Journal or Publication Title: Molecular cell
Volume of the journal: 54
Issue Number: 6
Abstract:

The carboxy-terminal binding protein (CtBP)-interacting protein (CtIP) is known to function in 5' strand resection during homologous recombination, similar to the budding yeast Sae2 protein, but its role in this process is unclear. Here, we characterize recombinant human CtIP and find that it exhibits 5' flap endonuclease activity on branched DNA structures, independent of the MRN complex. Phosphorylation of CtIP at known damage-dependent sites and other sites is essential for its catalytic activity, although the S327 and T847 phosphorylation sites are dispensable. A catalytic mutant of CtIP that is deficient in endonuclease activity exhibits wild-type levels of homologous recombination at restriction enzyme-generated breaks but is deficient in processing topoisomerase adducts and radiation-induced breaks in human cells, suggesting that the nuclease activity of CtIP is specifically required for the removal of DNA adducts at sites of DNA breaks.

Divisions: 10 Department of Biology
10 Department of Biology > Radiation Biology and DNA Repair
Date Deposited: 27 May 2014 11:28
Last Modified: 11 Sep 2014 08:12
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