TY - JOUR T1 - Proper chromosome alignment depends on BRCA2 phosphorylation by PLK1 JF - bioRxiv DO - 10.1101/265934 SP - 265934 AU - Åsa Ehlén AU - Charlotte Martin AU - Simona Miron AU - Manon Julien AU - François-Xavier Theillet AU - Virginie Boucherit AU - Virginie Ropars AU - Patricia Duchambon AU - Ahmed El Marjou AU - Sophie Zinn-Justin AU - Aura Carreira Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/04/08/265934.abstract N2 - 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. ER -