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

K J Abel1, J Xu, G Y Yin

  • 1Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor 48109-0674, USA.

Human Molecular Genetics
|December 1, 1995
PubMed
Summary

Researchers isolated the mouse BRCA1 gene (Brac1), homologous to the human gene linked to breast and ovarian cancer. Conserved domains suggest critical functions in DNA binding and transcription regulation.

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Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • The human BRCA1 gene is associated with hereditary breast and ovarian cancer.
  • Isolation of the human BRCA1 gene has been recently reported.

Purpose of the Study:

  • To isolate and characterize the murine homolog of the human BRCA1 gene, named Brac1.
  • To analyze the sequence, protein homology, and genomic localization of Brac1.

Main Methods:

  • cDNA isolation and sequencing of the murine Brac1 gene.
  • Bioinformatic analysis of predicted protein sequence and homology with human BRCA1.
  • Genomic mapping of the Brac1 gene using an interspecific backcross panel.

Main Results:

  • The mouse Brac1 cDNA predicts a protein of 1812 amino acids, showing 58% identity and 73% similarity to human BRCA1.

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  • Highly conserved regions, including a RING finger domain and an acidic domain, were identified at the amino and carboxyl termini, respectively.
  • Brac1 was mapped to mouse chromosome 11, in a region syntenic to human chromosome 17q21.

    • Conclusions:

    • The high conservation of Brac1 with human BRCA1, particularly in functional domains, underscores its importance in mammalian evolution.
    • Conserved domains suggest potential roles in DNA/protein binding and transcriptional regulation.
    • The isolated Brac1 sequence and cDNAs are valuable tools for further research into BRCA1 function and its role in cancer.