Proper chromosome alignment depends on BRCA2 phosphorylation by PLK1

Åsa Ehlén, Charlotte Martin, Simona Miron, Manon Julien, François-Xavier Theillet, Virginie Ropars, Gaetana Sessa, Romane Beaurepere, Virginie Boucherit, Patricia Duchambon, Ahmed El Marjou, Sophie Zinn-Justin () and Aura Carreira ()
Additional contact information
Åsa Ehlén: PSL Research University, CNRS, UMR3348
Charlotte Martin: PSL Research University, CNRS, UMR3348
Simona Miron: CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay
Manon Julien: CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay
François-Xavier Theillet: CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay
Virginie Ropars: CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay
Gaetana Sessa: PSL Research University, CNRS, UMR3348
Romane Beaurepere: PSL Research University, CNRS, UMR3348
Virginie Boucherit: PSL Research University, CNRS, UMR3348
Patricia Duchambon: Institut Curie
Ahmed El Marjou: Institut Curie
Sophie Zinn-Justin: CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay
Aura Carreira: PSL Research University, CNRS, UMR3348

Nature Communications, 2020, vol. 11, issue 1, 1-21

Abstract: Abstract 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 identify a conserved phosphorylation site at T207 of BRCA2 that constitutes a bona fide docking site for PLK1 and is phosphorylated in mitotic cells. We show 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 unstable kinetochore-microtubule interactions, misaligned chromosomes, faulty chromosome segregation and aneuploidy. We thus reveal a 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-15689-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15689-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-15689-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().