Roles of Breast Cancer Genes in DNA Homologous Recombination and Cellular Sensitivity to Radiation and Anticancer Drugs

Abstract

Mutations of the BRCA2 and BRCAl tumor suppressor genes predispose humans to many forms of cancer, including breast and ovarian cancer. It has been suggested that BRCAl and BRCA2 may serve as "caretakers" to repair DNA by interacting with RAD5 1. It is also possible that BRCAl and BRCA2 interact with additional proteins to accomplish their functional roles in tumor suppression. We have focused our study on BRCA2. The first objective is to further characterize the role of BRCA2 in DNA homologous recombination and cellular sensitivity to DNA damage. Although the interactions between exon 11 of human BRCA2 with RAD5l have been extensively reported, little is known about the interaction between RAD5 1 and the C-terminal domain coded by exon 27 of BRCA2. We clarified the interaction between RAD5l and this C-terminal region of human BRCA2, and further demonstrated that its overexpression inhibits DNA double strand break-induced homologous recombination. The second objective is to identify new proteins that may interact with BRCA2. We have identified two new BRCA2-interacting proteins, BCClP and ABP-280/filamin-l. We have performed extensive characterization on these interactions and published 2 papers and submitted another.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 2002
Accession Number
ADB284977

Entities

People

  • Zhiyuan Shen

Organizations

  • University of New Mexico

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Anti-Bacterial Agents
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Chromosomes
  • Confocal Microscopy
  • Genetic Structures
  • Genetics
  • Health Services
  • Infection
  • Medical Personnel
  • Neoplasms
  • Proteins
  • Tumor Cell Line

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Molecular and genetic basis of cancer.