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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2002-3-5
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pubmed:databankReference |
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pubmed:abstractText |
Brca1 C-terminal (BRCT) domains are a common protein-protein interaction motif in proteins involved in the DNA damage response and DNA repair. The DNA-damage response protein 53BP1 has two BRCT domains that bind to the DNA-binding domain of p53. The 53BP1 tandem-BRCT region is homologous to the tandem-BRCT region of Brca1, which is involved in double-strand break repair and homologous recombination and which binds BACH1, a member of the DEAH helicase family. Here we report the structures of a human 53BP1-p53 complex and of the rat Brca1 BRCT repeats. The 53BP1-p53 structure shows that the two BRCT repeats are arranged tandemly and pack extensively through an interface that also involves the inter-repeat linker. The first BRCT repeat and the linker together bind p53 on a region that overlaps with the DNA-binding surface of p53 and involves p53 residues that are mutated in cancer and are important for DNA binding. Comparison with the structure of the tandem-BRCT region of Brca1 shows a remarkable conservation of the repeat arrangement and of the inter-BRCT repeat interface. Analysis of human BRCA1 tumor-derived mutations and conservation identifies a potential protein-binding site that we show through mutagenesis is involved in BACH1 binding. The BACH1-binding region of Brca1 consists of a unique insertion in the first BRCT repeat and the inter-repeat linker and is analogous to the region of 53BP1 that binds p53.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-10196224,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-10426999,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-10549283,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-10550055,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-10724175,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-10783165,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-10801407,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-10928918,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-11042216,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-11114888,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-11134068,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-11238909,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-11242102,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-11301010,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-11331310,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-11406561,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-11504724,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-11573086,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-7510367,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-7969167,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-8016121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-8023157,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-8532526,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-8673121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-8875926,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-8910340,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-9000507,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-9034168,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-9136882,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-9267023,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-9407031,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-9461304,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-9705934,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-9738006,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-9751050,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-9799248,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11877378-9973609
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0890-9369
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
583-93
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:11877378-Amino Acid Sequence,
pubmed-meshheading:11877378-Animals,
pubmed-meshheading:11877378-BRCA1 Protein,
pubmed-meshheading:11877378-Carrier Proteins,
pubmed-meshheading:11877378-Humans,
pubmed-meshheading:11877378-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:11877378-Models, Molecular,
pubmed-meshheading:11877378-Molecular Sequence Data,
pubmed-meshheading:11877378-Phosphoproteins,
pubmed-meshheading:11877378-Rats,
pubmed-meshheading:11877378-Sequence Homology, Amino Acid,
pubmed-meshheading:11877378-Tumor Suppressor Protein p53
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pubmed:year |
2002
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pubmed:articleTitle |
Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure.
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pubmed:affiliation |
Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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