Nat Struct Biol. 2001 Oct;8(10):838-42.

Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1.

Source

Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.

Abstract

The C-terminal BRCT region of BRCA1 is essential for its DNA repair, transcriptional regulation and tumor suppressor functions. Here we determine the crystal structure of the BRCT domain of human BRCA1 at 2.5 A resolution. The domain contains two BRCT repeats that adopt similar structures and are packed together in a head-to-tail arrangement. Cancer-causing missense mutations occur at the interface between the two repeats and destabilize the structure. The manner by which the two BRCT repeats interact in BRCA1 may represent a general mode of interaction between homologous domains within proteins that interact to regulate the cellular response to DNA damage. The structure provides a basis to predict the structural consequences of uncharacterized BRCA1 mutations.

Comment in

With the ends in sight: images from the BRCA1 tumor suppressor. [Nat Struct Biol. 2001]
With the ends in sight: images from the BRCA1 tumor suppressor.Baer R. Nat Struct Biol. 2001 Oct; 8(10):822-4.

PMID:: 11573086; [PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms, Substances, Secondary Source ID

Publication Types

Research Support, Non-U.S. Gov't

MeSH Terms

Substances

BRCA1 Protein

Secondary Source ID

PDB/1JNX

LinkOut - more resources

Full Text Sources

Medical

BRCA1 Gene - Genetics Home Reference

Miscellaneous

See the articles recommended by F1000Prime's Faculty of 5,000 renowned researchers and clinicians, assisted by 5,000 associates. - F1000

Supplemental Content

Save items

Related citations in PubMed

Structure of the BRCT repeats of BRCA1 bound to a BACH1 phosphopeptide: implications for signaling. [Mol Cell. 2004]
Structure of the BRCT repeats of BRCA1 bound to a BACH1 phosphopeptide: implications for signaling.
Shiozaki EN, Gu L, Yan N, Shi Y. Mol Cell. 2004 May 7; 14(3):405-12.
Structural consequences of a cancer-causing BRCA1-BRCT missense mutation. [J Biol Chem. 2003]
Structural consequences of a cancer-causing BRCA1-BRCT missense mutation.
Williams RS, Glover JN. J Biol Chem. 2003 Jan 24; 278(4):2630-5. Epub 2002 Nov 8.
Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1. [Nat Struct Mol Biol. 2004]
Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1.
Williams RS, Lee MS, Hau DD, Glover JN. Nat Struct Mol Biol. 2004 Jun; 11(6):519-25. Epub 2004 May 9.
Review Insights into the molecular basis of human hereditary breast cancer from studies of the BRCA1 BRCT domain. [Fam Cancer. 2006]
Review Insights into the molecular basis of human hereditary breast cancer from studies of the BRCA1 BRCT domain.
Glover JN. Fam Cancer. 2006; 5(1):89-93.
Review Interactions between BRCT repeats and phosphoproteins: tangled up in two. [Trends Biochem Sci. 2004]
Review Interactions between BRCT repeats and phosphoproteins: tangled up in two.
Glover JN, Williams RS, Lee MS. Trends Biochem Sci. 2004 Nov; 29(11):579-85.

See reviews... See all...

Cited by 51 PubMed Central articles

Functional and Structural Analysis of C-Terminal BRCA1 Missense Variants. [PLoS One. 2013]
Functional and Structural Analysis of C-Terminal BRCA1 Missense Variants.
Quiles F, Fernández-Rodríguez J, Mosca R, Feliubadaló L, Tornero E, Brunet J, Blanco I, Capellá G, Pujana MÀ, Aloy P, et al. PLoS One. 2013; 8(4):e61302. Epub 2013 Apr 17.
Structure-Function Of The Tumor Suppressor BRCA1. [Comput Struct Biotechnol J. 2012]
Structure-Function Of The Tumor Suppressor BRCA1.
Clark SL, Rodriguez AM, Snyder RR, Hankins GD, Boehning D. Comput Struct Biotechnol J. 2012 Apr 1; 1(1).
Homologs of breast cancer genes in plants. [Front Plant Sci. 2011]
Homologs of breast cancer genes in plants.
Trapp O, Seeliger K, Puchta H. Front Plant Sci. 2011; 2:19. Epub 2011 Jun 20.

See all...

Structures reported by this article

Crystal Structure Of The Brct Repeat Region From The Breast Cancer Associated Protein, Brca1

PDB: 1JNX

Source: Homo sapiens

Method: X-Ray Diffraction

Resolution: 2.5 Å

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
Gene
Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
Gene (GeneRIF)
Gene records that have the current articles as Reference into Function citations (GeneRIFs). NLM staff reviewing the literature while indexing MEDLINE add GeneRIFs manually.
HomoloGene
HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
Nucleotide (RefSeq)
NCBI nucleotide Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Nucleotide (Weighted)
Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.
OMIM (calculated)
Online Mendelian Inheritance in Man (OMIM) records that include the current articles as references in the light bulb links within or in the citations at the end of the OMIM record. The references available through the light bulb link are collected using the PubMed related articles algorithm to identify records with similar terminology to the OMIM record.
Protein (RefSeq)
NCBI protein Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Protein (Weighted)
Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.
Protein Clusters
Clusters of related proteins from the Protein Clusters database that cite the current articles. Sources of references in Protein Clusters include the associated Gene and Conserved Domain records as well as NCBI added citations.
Taxonomy via GenBank
Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).
UniGene
UniGene clusters of expressed sequences that are associated with the current articles through references on the clustered sequence records and related Gene records.
Domains
Conserved Domain Database (CDD) records that cite the current articles. Citations are from the CDD source database records (PFAM, SMART).
Protein
Protein translation features of primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
Structure
Three-dimensional structure records in the NCBI Structure database for data reported in the current articles.
GEO Profiles
Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

Crystal structure of the BRCT repeat region from the breast cancer-associated pr...
Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1.
Nat Struct Biol. 2001 Oct ;8(10):838-42.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to: