The cohesin complex is required for the DNA damage-induced G2/M checkpoint in mammalian cells.
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.
Watrin
Erwan
E
Research Institute of Molecular Pathology (IMP), Vienna, Austria.
Peters
Jan-Michael
JM
D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology*; D016195:G2 Phase; D018816:Genes, cdc; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012854:Sister Chromatid Exchange; D000097722:Cohesins
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D021122:Protein Subunits; D000097722:Cohesins