Understanding the functions of BRCA1 in the DNA-damage response

Maximina H. Yun, Kevin Hiom

    Research output: Contribution to journalReview article

    31 Citations (Scopus)

    Abstract

    Inheritance of a mutation in BRCA1 (breast cancer 1 early-onset) results in predisposition to early-onset breast and ovarian cancer. Tumours in these individuals arise after somatic mutation or loss of the wild-type allele. Loss of BRCA1 function leads to a profound increase in genomic instability involving the accumulation of mutations, DNA breaks and gross chromosomal rearrangements. Accordingly, BRCA1 has been implicated as an important factor involved in both the repair of DNA lesions and in the regulation of cell-cycle checkpoints in response to DNA damage. However, the molecular mechanism through which BRCA1 functions to preserve genome stability remains unclear. in the present article, we examine the different ways in which BRCA1 might influence the repair of DNA damage and the preservation of genome integrity, taking into account what is currently known about its interactions with other proteins, its biochemical activity and its nuclear localization.

    Original languageEnglish
    Pages (from-to)597-604
    Number of pages8
    JournalBiochemical Society Transactions
    Volume37
    DOIs
    Publication statusPublished - Jun 2009

    Keywords

    • breast cancer 1 early-onset (BRCA1)
    • DNA-damage response
    • double-strand break
    • Fanconi's anaemia
    • homologous recombination
    • ubiquitination
    • STRAND BREAK ENDS
    • CROSS-LINK REPAIR
    • HOMOLOGOUS RECOMBINATION
    • CAENORHABDITIS-ELEGANS
    • TUMOR SUSCEPTIBILITY
    • UBIQUITIN STRUCTURES
    • GENOMIC STABILITY
    • LIGASE ACTIVITY
    • OVARIAN-CANCER
    • TARGETS BRCA1

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