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Interaction between DNA Polymerase β and BRCA1

Public Library of Science
Publication Date
DOI: 10.1371/journal.pone.0066801
  • Research Article
  • Biology
  • Biochemistry
  • Nucleic Acids
  • Dna
  • Dna Modification
  • Dna Repair
  • Dna Synthesis
  • Proteins
  • Protein Interactions
  • Genetics
  • Cancer Genetics
  • Immunology
  • Immunologic Techniques
  • Immunoassays
  • Immunofluorescence
  • Molecular Cell Biology
  • Medicine
  • Obstetrics And Gynecology
  • Breast Cancer
  • Oncology
  • Cancers And Neoplasms
  • Breast Tumors
  • Basic Cancer Research
  • Cancer Risk Factors
  • Biology


The breast cancer 1 (BRCA1) protein is a tumor suppressor playing roles in DNA repair and cell cycle regulation. Studies of DNA repair functions of BRCA1 have focused on double-strand break (DSB) repair pathways and have recently included base excision repair (BER). However, the function of BRCA1 in BER is not well defined. Here, we examined a BRCA1 role in BER, first in relation to alkylating agent (MMS) treatment of cells and the BER enzyme DNA polymerase β (pol β). MMS treatment of BRCA1 negative human ovarian and chicken DT40 cells revealed hypersensitivity, and the combined gene deletion of BRCA1 and pol β in DT40 cells was consistent with these factors acting in the same repair pathway, possibly BER. Using cell extracts and purified proteins, BRCA1 and pol β were found to interact in immunoprecipitation assays, yet in vivo and in vitro assays for a BER role of BRCA1 were negative. An alternate approach with the human cells of immunofluorescence imaging and laser-induced DNA damage revealed negligible BRCA1 recruitment during the first 60 s after irradiation, the period typical of recruitment of pol β and other BER factors. Instead, 15 min after irradiation, BRCA1 recruitment was strong and there was γ-H2AX co-localization, consistent with DSBs and repair. The rapid recruitment of pol β was similar in BRCA1 positive and negative cells. However, a fraction of pol β initially recruited remained associated with damage sites much longer in BRCA1 positive than negative cells. Interestingly, pol β expression was required for BRCA1 recruitment, suggesting a partnership between these repair factors in DSB repair.

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