Tumor Suppression by BRCA-1: A Critical Role at DNA Replication Forks

Abstract

BRCA1 is the major breast cancer susceptibility gene. It forms heterodimers with BARD1. Inactivation of either gene results in identical phenotypes suggesting that these proteins function primarily as a complex. BRCA1 deficiencies are associated with cellular phenotypes consistent with a DNA replication defect. We wished to test the hypothesis that BRCA1/BARD1 function during DNA replication supporting DNA transactions at replication forks. We are using cell-free extracts derived from Xenopus laevis eggs that support: 1. Semi-conservative, cell-cycle regulated DNA replication; 2. Many facets of the DNA damage response. Our key accomplishments were to generate specific antibodies against Xenopus BARD1 and BRCA1. We also demonstrate that the complex assembles to chromatin in a DNA replication-dependent manner. Finally, we show that BRCA1/BARD1 loading to chromatin does not dramatically increases following DNA damage, suggesting that it might be relocalized within chromatin compartments.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2006
Accession Number
ADA463242

Entities

People

  • Jean Gautier

Organizations

  • Columbia University

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Antibodies
  • Assembly
  • Biological Sciences
  • Biomedical Research
  • Breast Cancer
  • Cell Physiological Processes
  • Cells
  • Chromosome Structures
  • Genes
  • Genetic Phenomena
  • Genetics
  • Genome
  • Neoplasms
  • New York
  • Phenotypes
  • Proteins

Fields of Study

  • Biology

Readers

  • Molecular Genetics
  • Oncology (Cancer Research).