Document Detail


Persistently bound Ku at DNA ends attenuates DNA end resection and homologous recombination.
MedLine Citation:
PMID:  22265216     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
DNA double strand breaks (DSBs) are repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). The DNA cell cycle stage and resection of the DSB ends are two key mechanisms which are believed to push DSB repair to the HR pathway. Here, we show that the NHEJ factor Ku80 associates with DSBs in S phase, when HR is thought to be the preferred repair pathway, and its dynamics/kinetics at DSBs is similar to those observed for Ku80 in non-S phase in mammalian cells. A Ku homolog from Mycobacterium tuberculosis binds to and is retained at DSBs in S phase and was used as a tool to determine if blocking DNA ends affects end resection and HR in mammalian cells. A decrease in DNA end resection, as marked by IR-induced RPA, BrdU, and Rad51 focus formation, and HR are observed when Ku deficient rodent cells are complemented with Mt-Ku. Together, this data suggests that Ku70/80 binds to DSBs in all cell cycle stages and is likely actively displaced from DSB ends to free the DNA ends for DNA end resection and thus HR to occur.
Authors:
Zhengping Shao; Anthony J Davis; Kazi R Fattah; Sairei So; Jingxin Sun; Kyung-Jong Lee; Lynn Harrison; Jun Yang; David J Chen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-01-20
Journal Detail:
Title:  DNA repair     Volume:  11     ISSN:  1568-7856     ISO Abbreviation:  DNA Repair (Amst.)     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-02-07     Completed Date:  2012-09-10     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  101139138     Medline TA:  DNA Repair (Amst)     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  310-6     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Nuclear / metabolism*
CHO Cells
Cricetinae
Cricetulus
DNA / metabolism*
DNA Breaks, Double-Stranded*
DNA Repair
DNA-Binding Proteins / metabolism*
Homologous Recombination / genetics*
Humans
Mice
Mycobacterium tuberculosis / metabolism
Protein Binding
Protein Transport
Rad51 Recombinase / metabolism
S Phase
Grant Support
ID/Acronym/Agency:
CA134991/CA/NCI NIH HHS; CA50519/CA/NCI NIH HHS; CA85693/CA/NCI NIH HHS; CA85693-9S1/CA/NCI NIH HHS; CA92584/CA/NCI NIH HHS; R01 CA085693/CA/NCI NIH HHS; R37 CA050519/CA/NCI NIH HHS; R37 CA050519-21/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Nuclear; 0/DNA-Binding Proteins; 0/Ku autoantigen; 9007-49-2/DNA; EC 2.7.7.-/Rad51 Recombinase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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