PT  - JOURNAL ARTICLE
AU  - Åsa Ehlén
AU  - Charlotte Martin
AU  - Simona Miron
AU  - Manon Julien
AU  - François-Xavier Theillet
AU  - Virginie Ropars
AU  - Gaetana Sessa
AU  - Romane Beaurepere
AU  - Virginie Boucherit
AU  - Patricia Duchambon
AU  - Ahmed El Marjou
AU  - Sophie Zinn-Justin
AU  - Aura Carreira
TI  - Proper chromosome alignment depends on BRCA2 phosphorylation by PLK1
AID  - 10.1101/265934
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 265934
4099  - http://biorxiv.org/content/early/2019/10/26/265934.short
4100  - http://biorxiv.org/content/early/2019/10/26/265934.full
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 found that BRCA2 bound to PLK1 forms a complex with the phosphatase PP2A and phosphorylated-BUBR1. Reducing BRCA2 binding to PLK1, as observed in BRCA2 breast cancer variants S206C and T207A, alters the tetrameric complex resulting in 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.