RT Journal Article
SR Electronic
T1 Proper chromosome alignment depends on BRCA2 phosphorylation by PLK1
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 265934
DO 10.1101/265934
A1 Åsa Ehlén
A1 Charlotte Martin
A1 Simona Miron
A1 Manon Julien
A1 François-Xavier Theillet
A1 Virginie Boucherit
A1 Virginie Ropars
A1 Patricia Duchambon
A1 Ahmed El Marjou
A1 Sophie Zinn-Justin
A1 Aura Carreira
YR 2019
UL http://biorxiv.org/content/early/2019/04/08/265934.abstract
AB The BRCA2 tumor suppressor protein is involved in the maintenance of genome integrity through its role in homologous recombination. In mitosis, BRCA2 is phosphorylated by Polo-like kinase 1 (PLK1). Here we describe how this phosphorylation contributes to the control of mitosis. We identified two highly conserved phosphorylation sites at S193 and T207 of BRCA2. Phosphorylated-T207 is a bona fide docking site for PLK1 as illustrated by the crystal structure of the BRCA2 peptide bound to PLK1 Polo-box domain. We find that BRCA2 is in complex with PLK1, phosphorylated-BUBR1 and the phosphatase PP2A. Precluding BRCA2 binding to PLK1, as observed in BRCA2 breast cancer variants, alters the tetrameric complex resulting in mitotic delay, misaligned chromosomes, faulty chromosome segregation and aneuploidy. We thus reveal a direct role of BRCA2 in the alignment of chromosomes, distinct from its DNA repair function, with important consequences on chromosome stability. These findings may explain in part the aneuploidy observed in BRCA2-mutated tumors.