RGD Reference Report - Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure. - Rat Genome Database

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Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure.

Authors: Joo, WS  Jeffrey, PD  Cantor, SB  Finnin, MS  Livingston, DM  Pavletich, NP 
Citation: Joo WS, etal., Genes Dev 2002 Mar 1;16(5):583-93.
RGD ID: 625542
Pubmed: PMID:11877378   (View Abstract at PubMed)
PMCID: PMC155350   (View Article at PubMed Central)
DOI: DOI:10.1101/gad.959202   (Journal Full-text)

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.

Objects referenced in this article
Gene Brca1 BRCA1, DNA repair associated Rattus norvegicus

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