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| '''Crystal Structure of the 53bp1 BRCT Region Complexed to Tumor Suppressor P53'''
| | ===Crystal Structure of the 53bp1 BRCT Region Complexed to Tumor Suppressor P53=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_11877378}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11877378 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_11877378}} |
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| ==Disease== | | ==Disease== |
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| [[Category: Tandem-brct and linker complexed with non-brct protein]] | | [[Category: Tandem-brct and linker complexed with non-brct protein]] |
| [[Category: Three-helix bundle]] | | [[Category: Three-helix bundle]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:22:57 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 11:23:40 2008'' |
