Altered DNA binding by the human Rad51-R150Q mutant found in breast cancer patients

Takako Ishida, Yoshimasa Takizawa, Isao Sakane, Hitoshi Kurumizaka

    Research output: Contribution to journalArticle

    11 Citations (Scopus)

    Abstract

    The human Rad51 protein (HsRad51) catalyzes homologous pairing and strand exchange between single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) during recombinational repair of double-stranded DNA breaks. An HsRad51 mutation that results in the substitution of Gln for Arg150 (R150Q) was found in bilateral breast cancer patients; however, the consequences of this R150Q mutation have not been elucidated. To determine how this HsRad51(R150Q) mutation affects HsRad51 function, in the present study, we purified the HsRad51(R150Q) mutant. The purified HsRad51(R150Q) was completely proficient in the ATP-hydrolyzing activity. A gel filtration analysis revealed that HsRad51(R150Q) also retained the polymer formation ability. In contrast, the ssDNA- and dsDNA-binding abilities of HsRad51(R150Q) were clearly reduced, as compared to those of HsRad51. These differences in the DNA-binding properties between HsRad51(R150Q) and HsRad51 may be important to account for the tumorigenesis in breast cancer patients with the HsRad51(R150Q) mutation.

    Original languageEnglish
    Pages (from-to)1374-1378
    Number of pages5
    JournalBiological and Pharmaceutical Bulletin
    Volume30
    Issue number8
    DOIs
    Publication statusPublished - 2007 Aug

    Fingerprint

    Breast Neoplasms
    Mutation
    Single-Stranded DNA
    Gel Chromatography
    Polymers
    Carcinogenesis
    Adenosine Triphosphate
    DNA
    Proteins

    Keywords

    • Breast cancer
    • DNA binding
    • DNA repair
    • Homologous recombination
    • Rad51
    • Tumorigenesis

    ASJC Scopus subject areas

    • Molecular Medicine
    • Pharmacology, Toxicology and Pharmaceutics(all)

    Cite this

    Altered DNA binding by the human Rad51-R150Q mutant found in breast cancer patients. / Ishida, Takako; Takizawa, Yoshimasa; Sakane, Isao; Kurumizaka, Hitoshi.

    In: Biological and Pharmaceutical Bulletin, Vol. 30, No. 8, 08.2007, p. 1374-1378.

    Research output: Contribution to journalArticle

    Ishida, Takako ; Takizawa, Yoshimasa ; Sakane, Isao ; Kurumizaka, Hitoshi. / Altered DNA binding by the human Rad51-R150Q mutant found in breast cancer patients. In: Biological and Pharmaceutical Bulletin. 2007 ; Vol. 30, No. 8. pp. 1374-1378.
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