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

Research output: Contribution to journalArticle

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 - May 2008
Externally publishedYes

Fingerprint

BRCA2 Protein
Peptides
Proteins
Recombinational DNA Repair
Amino Acids
Neoplasms
DNA
Radiotherapy
Drug Therapy

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Nomme, J., Takizawa, Y., Martinez, S. F., Renodon-Cornière, A., Fleury, F., Weigel, P., ... 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

Inhibition of filament formation of human Rad51 protein by a small peptide derived from the BRC-motif of the BRCA2 protein. / Nomme, Julian; Takizawa, Yoshimasa; Martinez, Susan F.; Renodon-Cornière, Axelle; Fleury, Fabrice; Weigel, Pierre; Yamamoto, Ken-ichi; Kurumizaka, Hitoshi; Takahashi, Masayuki.

In: Genes to Cells, Vol. 13, No. 5, 05.2008, p. 471-481.

Research output: Contribution to journalArticle

Nomme, J, Takizawa, Y, Martinez, SF, Renodon-Cornière, A, Fleury, F, Weigel, P, Yamamoto, K, 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, vol. 13, no. 5, pp. 471-481. https://doi.org/10.1111/j.1365-2443.2008.01180.x
Nomme, Julian ; Takizawa, Yoshimasa ; Martinez, Susan F. ; Renodon-Cornière, Axelle ; Fleury, Fabrice ; Weigel, Pierre ; Yamamoto, Ken-ichi ; Kurumizaka, Hitoshi ; Takahashi, Masayuki. / Inhibition of filament formation of human Rad51 protein by a small peptide derived from the BRC-motif of the BRCA2 protein. In: Genes to Cells. 2008 ; Vol. 13, No. 5. pp. 471-481.
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