C. ChalermrujinanantW. MichowskiG. SittithumchareeF. EsashiS. JirawatnotaiMahidol UniversityDana-Farber Cancer InstituteSir William Dunn School of Pathology2018-12-112019-03-142018-12-112019-03-142016-06-02Oncogene. Vol.35, No.22 (2016), 2815-282314765594095092322-s2.0-84973340610https://repository.li.mahidol.ac.th/handle/20.500.14594/43014© 2016 Macmillan Publishers Limited. BRCA2 has an important role in the maintenance of genome stability by interacting with RAD51 recombinase through its C-terminal domain. This interaction is abrogated by cyclin A-CDK2-mediated phosphorylation of BRCA2 at serine 3291 (Ser3291). Recently, we showed that cyclin D1 facilitates RAD51 recruitment to BRCA2-containing DNA repair foci, and that downregulation of cyclin D1 leads to inefficient homologous-mediated DNA repair. Here, we demonstrate that cyclin D1, via amino acids 20-90, interacts with the C-terminal domain of BRCA2, and that this interaction is increased in response to DNA damage. Interestingly, CDK4-cyclin D1 does not phosphorylate Ser3291. Instead, cyclin D1 bars cyclin A from the C-terminus of BRCA2, prevents cyclin A-CDK2-dependent Ser3291 phosphorylation and facilitates RAD51 binding to the C-terminal domain of BRCA2. These findings indicate that the interplay between cyclin D1 and other cyclins such as cyclin A regulates DNA integrity through RAD51 interaction with the BRCA2 C-terminal domain.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1038/onc.2015.354