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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2011-4-11
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pubmed:abstractText |
The tumor suppressor protein BRCA1 is a constituent of several different protein complexes and is required for homology-directed repair (HDR) of DNA double strand breaks (DSBs). The most recently discovered BRCA1-RAP80 complex is recruited to ubiquitin structures on chromatin surrounding the break. Deficiency of any member of this complex confers hypersensitivity to DNA-damaging agents by undefined mechanisms. In striking contrast to other BRCA1-containing complexes that are known to promote HDR, we demonstrate that the BRCA1-RAP80 complex restricts end resection in S/G(2) phase of the cell cycle, thereby limiting HDR. RAP80 or BRCC36 deficiency resulted in elevated Mre11-CtIP-dependent 5' end resection with a concomitant increase in HDR mechanisms that rely on 3' single-stranded overhangs. We propose a model in which the BRCA1-RAP80 complex limits nuclease accessibility to DSBs, thus preventing excessive end resection and potentially deleterious homology-directed DSB repair mechanisms that can impair genome integrity.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/BRCA1 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/BRCA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BRCC3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/MRE11A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Multiprotein Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RAP80 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/RBBP8 protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1083-351X
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
286
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13669-80
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pubmed:meshHeading |
pubmed-meshheading:21335604-BRCA1 Protein,
pubmed-meshheading:21335604-Carrier Proteins,
pubmed-meshheading:21335604-Chromatin,
pubmed-meshheading:21335604-DNA Breaks, Double-Stranded,
pubmed-meshheading:21335604-DNA Repair,
pubmed-meshheading:21335604-DNA-Binding Proteins,
pubmed-meshheading:21335604-G2 Phase,
pubmed-meshheading:21335604-Genomic Instability,
pubmed-meshheading:21335604-HeLa Cells,
pubmed-meshheading:21335604-Humans,
pubmed-meshheading:21335604-Membrane Proteins,
pubmed-meshheading:21335604-Multiprotein Complexes,
pubmed-meshheading:21335604-Nuclear Proteins,
pubmed-meshheading:21335604-S Phase
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pubmed:year |
2011
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pubmed:articleTitle |
The BRCA1-RAP80 complex regulates DNA repair mechanism utilization by restricting end resection.
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pubmed:affiliation |
Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6160, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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