Understanding the functions of BRCA1 in the DNA-damage response

Maximina H. Yun, Kevin Hiom

    Research output: Contribution to journalReview article

    29 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

    Cite this

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    title = "Understanding the functions of BRCA1 in the DNA-damage response",
    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.",
    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",
    author = "Yun, {Maximina H.} and Kevin Hiom",
    year = "2009",
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    doi = "10.1042/BST0370597",
    language = "English",
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    journal = "Biochemical Society Transactions",
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    Understanding the functions of BRCA1 in the DNA-damage response. / Yun, Maximina H.; Hiom, Kevin.

    In: Biochemical Society Transactions, Vol. 37, 06.2009, p. 597-604.

    Research output: Contribution to journalReview article

    TY - JOUR

    T1 - Understanding the functions of BRCA1 in the DNA-damage response

    AU - Yun, Maximina H.

    AU - Hiom, Kevin

    PY - 2009/6

    Y1 - 2009/6

    N2 - 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.

    AB - 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.

    KW - breast cancer 1 early-onset (BRCA1)

    KW - DNA-damage response

    KW - double-strand break

    KW - Fanconi's anaemia

    KW - homologous recombination

    KW - ubiquitination

    KW - STRAND BREAK ENDS

    KW - CROSS-LINK REPAIR

    KW - HOMOLOGOUS RECOMBINATION

    KW - CAENORHABDITIS-ELEGANS

    KW - TUMOR SUSCEPTIBILITY

    KW - UBIQUITIN STRUCTURES

    KW - GENOMIC STABILITY

    KW - LIGASE ACTIVITY

    KW - OVARIAN-CANCER

    KW - TARGETS BRCA1

    U2 - 10.1042/BST0370597

    DO - 10.1042/BST0370597

    M3 - Review article

    VL - 37

    SP - 597

    EP - 604

    JO - Biochemical Society Transactions

    JF - Biochemical Society Transactions

    SN - 0300-5127

    ER -