Inhibition of filament formation of human Rad51 protein by a small peptide derived from the BRC-motif of the BRCA2 protein

Julian Nomme, Yoshimasa Takizawa, Susan F. Martinez, Axelle Renodon-Cornière, Fabrice Fleury, Pierre Weigel, Ken Ichi Yamamoto, Hitoshi Kurumizaka, Masayuki Takahashi

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    28 Citations (Scopus)

    Abstract

    Human Rad51 is a key element of recombinational DNA repair and is related to the resistance of cancer cells to chemo- and radiotherapies. The protein is thus a potential target of anti-cancer treatment. The crystallographic analysis shows that the BRC-motif of the BRCA2 tumor suppressor is in contact with the subunit-subunit interface of Rad51 and could thus prevent filament formation of Rad51. However, biochemical analysis indicates that a BRC-motif peptide of 69 amino acids preferentially binds to the N-terminal part of Rad51. We show experimentally that a short peptide of 28 amino acids derived from the BRC4 motif binds to the subunit-subunit interface and dissociates its filament, both in the presence and absence of DNA, certainly by binding to dissociated monomers. The inhibition is efficient and specific for Rad51: the peptide does not even interact with Rad51 homologs or prevent their interaction with DNA. Neither the N-terminal nor the C-terminal half of the peptide interacts with human Rad51, indicating that both parts are involved in the interaction, as expected from the crystal structure. These results suggest the possibility of developing inhibitors of human Rad51 based on this peptide.

    Original languageEnglish
    Pages (from-to)471-481
    Number of pages11
    JournalGenes to Cells
    Volume13
    Issue number5
    DOIs
    Publication statusPublished - 2008 May

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    ASJC Scopus subject areas

    • Genetics
    • Cell Biology

    Cite this

    Nomme, J., Takizawa, Y., Martinez, S. F., Renodon-Cornière, A., Fleury, F., Weigel, P., Yamamoto, K. I., Kurumizaka, H., & Takahashi, M. (2008). Inhibition of filament formation of human Rad51 protein by a small peptide derived from the BRC-motif of the BRCA2 protein. Genes to Cells, 13(5), 471-481. https://doi.org/10.1111/j.1365-2443.2008.01180.x