title: SUMOylation of the α-kleisin subunit of cohesin is required for DNA damage-induced cohesion.
abstract: BACKGROUND
  Cohesion between sister chromatids is fundamental to ensure faithful chromosome segregation during mitosis and accurate repair of DNA damage postreplication. At the molecular level, cohesion establishment involves two defined events, a chromatin binding step and a chromatid entrapment event driven by posttranslational modifications on cohesin subunits.
  
  
  RESULTS
  Here, we show that modification by the small ubiquitin-like protein (SUMO) is required for sister chromatid tethering after DNA damage. We find that all subunits of cohesin become SUMOylated upon exposure to DNA damaging agents or presence of a DNA double-strand break. We have mapped all lysine residues on cohesin's α-kleisin subunit Mcd1 (Scc1) where SUMO can conjugate. We demonstrate that Mcd1 SUMOylation-deficient alleles are still recruited to DSB-proximal regions but are defective in tethering sister chromatids and consequently fail to establish damage-induced cohesion both at DSBs and undamaged chromosomes. Moreover, we demonstrate that the bulk of Mcd1 SUMOylation in response to damage is carried out by the SUMO E3 ligase Nse2, a subunit of the related Smc5-Smc6 complex. SUMOylation occurs in cells with compromised Chk1 kinase activity, necessary for known posttranslational modifications on Mcd1, required for damage-induced cohesion.
  
  
  CONCLUSIONS
  These findings demonstrate that SUMOylation of Mcd1 is a novel prerequisite for the establishment of DNA damage-induced cohesion at DSB-proximal regions and cohesion-associating regions (CARs) genome-wide.
authors: Cell Cycle Group, MRC Clinical Sciences Centre, Imperial College, Du Cane Road, London W12 0NN, UK.
authors: Alexandra
authors: A
authors: McAleenan
authors: Violeta
authors: V
authors: Cordon-Preciado
authors: Andres
authors: A
authors: Clemente-Blanco
authors: I-Chun
authors: IC
authors: Liu
authors: Nicholas
authors: N
authors: Sen
authors: Joanne
authors: J
authors: Leonard
authors: Adam
authors: A
authors: Jarmuz
authors: Luis
authors: L
authors: Aragón
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism* / Q000502:physiology; D002842:Chromatids / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism* / Q000502:physiology; D020090:Chromosome Segregation / Q000502:physiology*; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology; D058207:Sumoylation; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C490529:MCD1 protein, S cerevisiae