Mouse Brca1: localization, sequence analysis and identification of evolutionarily conserved domains

The human gene BRCA1, conferring susceptibility to early-onset breast and ovarian cancer, has recently been isolated. Here we describe isolation of cDNAs, sequence analysis, and genomic localization of the murine homolog, Brca1. The mouse cDNA sequence predicts a protein of 1812 amino acids; a numbe...

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Bibliographic Details
Published in:Human molecular genetics 1995-12, Vol.4 (12), p.2265-2273
Main Authors: Abel, Kenneth J., Xu, Junzhe, Yin, Gui-Ying, Lyons, Robert H., Meisler, Miriam H., Weber, Barbara L.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Biological and medical sciences
Biological Evolution
BRCA1 Protein
Conserved Sequence
DNA, Complementary - isolation & purification
Fundamental and applied biological sciences. Psychology
Genes. Genome
Humans
Mice
Mice, Inbred C57BL
Molecular and cellular biology
Molecular genetics
Molecular Sequence Data
Neoplasm Proteins - genetics
RNA, Messenger - genetics
Sequence Homology, Amino Acid
Transcription Factors - genetics
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Summary:The human gene BRCA1, conferring susceptibility to early-onset breast and ovarian cancer, has recently been isolated. Here we describe isolation of cDNAs, sequence analysis, and genomic localization of the murine homolog, Brca1. The mouse cDNA sequence predicts a protein of 1812 amino acids; a number of small gaps account for the 51 fewer residues in the mouse protein relative to human BRCA1. While the predicted mouse and human proteins display on the whole a high level of homology (58% identity, 73% similarity), the regions of greatest homology are at the respective amino and carboxyl termini. Most reported disease-associated missense mutations in human BRCA1 occurred within these more highly conserved terminal regions. A predicted zinc-binding RING finger domain near the amino terminus lies within a 50 amino acid stretch that is perfectly conserved in both species. The strong conservation during mammalian evolution argues for the importance of this domain, perhaps mediating a role for BRCA1 in DNA and/or protein binding. We have also identified a conserved highly acidic domain in the carboxyl terminal half of the BRCA1 protein resembling acidic transactivation domains of certain transcription factors. Using an interspecific backcross panel, Brca1 was mapped to a region of mouse chromosome 11 that exhibits conserved linkage with human 17q21. The sequence and isolated cDNAs will provide useful reagents for studying the expression of Brca1 in the mouse, and for testing the importance of the evolutionarily conserved domains.
ISSN:0964-6906
1460-2083
DOI:10.1093/hmg/4.12.2265