The kleisin subunit of cohesin dictates damage-induced cohesion.
Cohesin, the protein complex that mediates sister chromatid cohesion, is required for faithful chromosome segregation and efficient repair of double-strand breaks (DSBs). Cohesion generation is normally restricted to S phase. However, in G2/M, a DSB activates cohesion generation near the DSB and genome-wide. Here, using budding yeast, we show that DSB-induced cohesion occurs when cohesin contains the kleisin subunit, Mcd1 (Scc1), but not when Mcd1 is replaced by its meiotic isoform, Rec8. We exploit this divergence to demonstrate that serine 83 of Mcd1 and the Chk1 kinase are critical determinants for DSB-induced cohesion. We propose that a DSB in G2/M activates Mec1 (ATR), which in turn stimulates Chk1-dependent phosphorylation of Mcd1 at serine 83. Serine 83 phosphorylation promotes chromatin-bound cohesin to become cohesive.
Heidinger-Pauli
Jill M
JM
Department of Embryology, Howard Hughes Medical Institute, Carnegie Institution, 3520 San Martin Drive, Baltimore, MD 21218, USA.
Unal
Elçin
E
Guacci
Vincent
V
Koshland
Douglas
D
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D000071877:Checkpoint Kinase 1; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D008954:Models, Biological; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D012854:Sister Chromatid Exchange; D013329:Structure-Activity Relationship; D000097722:Cohesins
D018797:Cell Cycle Proteins; D000071877:Checkpoint Kinase 1; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D011494:Protein Kinases; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine; D000097722:Cohesins; C490529:MCD1 protein, S cerevisiae; C502898:REC8 protein, S cerevisiae