title: Scc1 sumoylation by Mms21 promotes sister chromatid recombination through counteracting Wapl.
abstract: DNA double-strand breaks (DSBs) fuel cancer-driving chromosome translocations. Two related structural maintenance of chromosomes (Smc) complexes, cohesin and Smc5/6, promote DSB repair through sister chromatid homologous recombination (SCR). Here we show that the Smc5/6 subunit Mms21 sumoylates multiple lysines of the cohesin subunit Scc1. Mms21 promotes cohesin-dependent small ubiquitin-like modifier (SUMO) accumulation at laser-induced DNA damage sites in S/G2 human cells. Cells expressing the nonsumoylatable Scc1 mutant (15KR) maintain sister chromatid cohesion during mitosis but are defective in SCR and sensitive to ionizing radiation (IR). Scc1 15KR is recruited to DNA damage sites. Depletion of Wapl, a negative cohesin regulator, rescues SCR defects of Mms21-deficient or Scc1 15KR-expressing cells. Expression of the acetylation-mimicking Smc3 mutant does not bypass the requirement for Mms21 in SCR. We propose that Scc1 sumoylation by Mms21 promotes SCR by antagonizing Wapl at a step after cohesin loading at DSBs and in a way not solely dependent on Smc3 acetylation.
authors: Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors: Nan
authors: N
authors: Wu
authors: Xiangduo
authors: X
authors: Kong
authors: Zhejian
authors: Z
authors: Ji
authors: Weihua
authors: W
authors: Zeng
authors: Patrick Ryan
authors: PR
authors: Potts
authors: Kyoko
authors: K
authors: Yokomori
authors: Hongtao
authors: H
authors: Yu
mesh_terms: D000107:Acetylation; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D002842:Chromatids; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins; D006801:Humans; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D058207:Sumoylation; D000097722:Cohesins
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D008025:Ligases; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; C429022:RAD21 protein, human; C488092:WAPL protein, human; D000097722:Cohesins; C503501:NSMCE2 protein, human