title: Extensive DNA damage-induced sumoylation contributes to replication and repair and acts in addition to the mec1 checkpoint.
abstract: The cellular response to DNA damage employs multiple dynamic protein modifications to exert rapid and adaptable effects. Substantial work has detailed the roles of canonical checkpoint-mediated phosphorylation in this program. Recent studies have also implicated sumoylation in the DNA damage response; however, a systematic view of the contribution of sumoylation to replication and repair and its interplay with checkpoints is lacking. Here, using a biochemical screen in yeast, we establish that DNA damage-induced sumoylation occurs on a large scale. We identify MRX (Mre11-Rad50-Xrs2) as a positive regulator of this induction for a subset of repair targets. In addition, we find that defective sumoylation results in failure to complete replication of a damaged genome and impaired DNA end processing, highlighting the importance of the SUMO-mediated response in genome integrity. We also show that DNA damage-induced sumoylation does not require Mec1 checkpoint signaling, and the presence of both enables optimal DNA damage resistance.
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Cremona
authors.forename: Prabha
authors.initials: P
authors.lastname: Sarangi
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hang
authors.forename: Sadia
authors.initials: S
authors.lastname: Rahman
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhao
mesh_terms: D059447:Cell Cycle Checkpoints; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism; D055786:Gene Knockout Techniques; D016681:Genome, Fungal; D042822:Genomic Instability; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D050296:Microbial Viability; D046912:Multiprotein Complexes / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D045643:DNA Repair Enzymes