title: Sumoylation influences DNA break repair partly by increasing the solubility of a conserved end resection protein.
abstract: Protein modifications regulate both DNA repair levels and pathway choice. How each modification achieves regulatory effects and how different modifications collaborate with each other are important questions to be answered. Here, we show that sumoylation regulates double-strand break repair partly by modifying the end resection factor Sae2. This modification is conserved from yeast to humans, and is induced by DNA damage. We mapped the sumoylation site of Sae2 to a single lysine in its self-association domain. Abolishing Sae2 sumoylation by mutating this lysine to arginine impaired Sae2 function in the processing and repair of multiple types of DNA breaks. We found that Sae2 sumoylation occurs independently of its phosphorylation, and the two modifications act in synergy to increase soluble forms of Sae2. We also provide evidence that sumoylation of the Sae2-binding nuclease, the Mre11-Rad50-Xrs2 complex, further increases end resection. These findings reveal a novel role for sumoylation in DNA repair by regulating the solubility of an end resection factor. They also show that collaboration between different modifications and among multiple substrates leads to a stronger biological effect.
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America; Programs in Biochemistry, Cell, and Molecular Biology, Weill Cornell Graduate School of Medical Sciences, New York, New York, United States of America.
authors.forename: Prabha
authors.initials: P
authors.lastname: Sarangi
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Roland
authors.initials: R
authors.lastname: Steinacher
authors.affiliation: Department of Biology, Masaryk University, Brno, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Altmannova
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biosciences, and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biosciences, and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Tanya T
authors.initials: TT
authors.lastname: Paull
authors.affiliation: Department of Biology, Masaryk University, Brno, Czech Republic; National Centre for Biomolecular Research, Masaryk University, Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital in Brno, Brno, Czech Republic.
authors.forename: Lumir
authors.initials: L
authors.lastname: Krejci
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Whitby
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America; Programs in Biochemistry, Cell, and Molecular Biology, Weill Cornell Graduate School of Medical Sciences, New York, New York, United States of America.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhao
mesh_terms: D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage / Q000235:genetics; D059766:DNA End-Joining Repair / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004706:Endodeoxyribonucleases / Q000235:genetics; D004720:Endonucleases / Q000235:genetics*; D005090:Exodeoxyribonucleases / Q000235:genetics; D006801:Humans; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D012995:Solubility; D058207:Sumoylation / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C086930:RAD50 protein, S cerevisiae; C107849:SAE2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C086929:XRS2 protein, S cerevisiae; D004706:Endodeoxyribonucleases; D004720:Endonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae