The cohesin complex is required for the DNA damage-induced G2/M checkpoint in mammalian cells. - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue EMBO Journal Année : 2009

The cohesin complex is required for the DNA damage-induced G2/M checkpoint in mammalian cells.

Résumé

Cohesin complexes mediate sister chromatid cohesion. Cohesin also becomes enriched at DNA double-strand break sites and facilitates recombinational DNA repair. Here, we report that cohesin is essential for the DNA damage-induced G2/M checkpoint. In contrast to cohesin's role in DNA repair, the checkpoint function of cohesin is independent of its ability to mediate cohesion. After RNAi-mediated depletion of cohesin, cells fail to properly activate the checkpoint kinase Chk2 and have defects in recruiting the mediator protein 53BP1 to DNA damage sites. Earlier work has shown that phosphorylation of the cohesin subunits Smc1 and Smc3 is required for the intra-S checkpoint, but Smc1/Smc3 are also subunits of a distinct recombination complex, RC-1. It was, therefore, unknown whether Smc1/Smc3 function in the intra-S checkpoint as part of cohesin. We show that Smc1/Smc3 are phosphorylated as part of cohesin and that cohesin is required for the intra-S checkpoint. We propose that accumulation of cohesin at DNA break sites is not only needed to mediate DNA repair, but also facilitates the recruitment of checkpoint proteins, which activate the intra-S and G2/M checkpoints.
Fichier principal
Vignette du fichier
inserm-00406182_edited.pdf (2.23 Mo) Télécharger le fichier
20966_1_merged_1245327621.pdf (13.86 Mo) Télécharger le fichier
20966_1_supp_228724_klfntl_convrt.pdf (1.69 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Origine : Fichiers produits par l'(les) auteur(s)
Format : Autre

Dates et versions

inserm-00406182 , version 1 (01-02-2010)

Identifiants

Citer

Erwan Watrin, Jan-Michael Peters. The cohesin complex is required for the DNA damage-induced G2/M checkpoint in mammalian cells.. EMBO Journal, 2009, 28 (17), pp.2625-35. ⟨10.1038/emboj.2009.202⟩. ⟨inserm-00406182⟩
103 Consultations
804 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More