The canine RAD51 mutation leads to the attenuation of interaction with PALB2

Mitsuki Uemura, Kazuhiko Ochiai, Masami Morimatsu, Masaki Michishita, Eri Onozawa, Daigo Azakami, Yumiko Uno, Yasunaga Yoshikawa, Takanori Sasaki, Masami Watanabe, Toshinori Omi

Research output: Contribution to journalArticle

Abstract

RAD51 forms a complex with BRCA2 and plays a central role in the DNA damage response pathway that is associated with homologous recombination. The structures of RAD51 and its homologues are highly conserved from prokaryotes to higher eukaryotes. Although a large number of BRCA2 mutations have been reported, there are only a few reports on the mutations of RAD51, which have been shown in humans and dogs. However, several mutations of canine RAD51 were identified from mammary gland tumour tissues in a recent study. Some of these mutations seem to have an influence on the homo-oligomerization or interaction with “Partner and localizer of BRCA2” (PALB2). In this study, we cloned the canine PALB2 homologue and investigated the effect on its interaction with the RAD51 mutants to evaluate the alteration in the function of RAD51 mutants. The A209S and T225S mutants of RAD51 show an attenuation of the interaction between RAD51 and PALB2. These results indicate that the canine RAD51 mutations can potentially alter the homologous recombination pathways in response to DNA damage in dogs.

Original languageEnglish
JournalVeterinary and Comparative Oncology
DOIs
Publication statusAccepted/In press - 2019

Keywords

  • BRCA2
  • DNA double-strand breaks (DSB)
  • cancer-associated single nucleotide polymorphisms (SNPs)
  • homologous recombination (HR)
  • mammary gland tumour

ASJC Scopus subject areas

  • veterinary(all)

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    Uemura, M., Ochiai, K., Morimatsu, M., Michishita, M., Onozawa, E., Azakami, D., Uno, Y., Yoshikawa, Y., Sasaki, T., Watanabe, M., & Omi, T. (Accepted/In press). The canine RAD51 mutation leads to the attenuation of interaction with PALB2. Veterinary and Comparative Oncology. https://doi.org/10.1111/vco.12542