title: Pro-recombination Role of Srs2 Protein Requires SUMO (Small Ubiquitin-like Modifier) but Is Independent of PCNA (Proliferating Cell Nuclear Antigen) Interaction.
abstract: Srs2 plays many roles in DNA repair, the proper regulation and coordination of which is essential. Post-translational modification by small ubiquitin-like modifier (SUMO) is one such possible mechanism. Here, we investigate the role of SUMO in Srs2 regulation and show that the SUMO-interacting motif (SIM) of Srs2 is important for the interaction with several recombination factors. Lack of SIM, but not proliferating cell nuclear antigen (PCNA)-interacting motif (PIM), leads to increased cell death under circumstances requiring homologous recombination for DNA repair. Simultaneous mutation of SIM in asrs2ΔPIMstrain leads to a decrease in recombination, indicating a pro-recombination role of SUMO. Thus SIM has an ambivalent function in Srs2 regulation; it not only mediates interaction with SUMO-PCNA to promote the anti-recombination function but it also plays a PCNA-independent pro-recombination role, probably by stimulating the formation of recombination complexes. The fact that deletion of PIM suppresses the phenotypes of Srs2 lacking SIM suggests that proper balance between the anti-recombination PCNA-bound and pro-recombination pools of Srs2 is crucial. Notably, sumoylation of Srs2 itself specifically stimulates recombination at the rDNA locus.
authors: From the Department of Biology and National Centre for Biomolecular Research, Masaryk University, 62500 Brno, Czech Republic.
authors: Peter
authors: P
authors: Kolesar
authors: From the Department of Biology and.
authors: Veronika
authors: V
authors: Altmannova
authors: the Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark, and.
authors: Sonia
authors: S
authors: Silva
authors: the Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark, and.
authors: Michael
authors: M
authors: Lisby
authors: From the Department of Biology and National Centre for Biomolecular Research, Masaryk University, 62500 Brno, Czech Republic, the International Clinical Research Center, Center for Biomolecular and Cellular Engineering, St. Anne's University Hospital in Brno, 60200 Brno, Czech Republic lkrejci@chemi.muni.cz.
authors: Lumir
authors: L
authors: Krejci
mesh_terms: D020816:Amino Acid Motifs; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism*; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic / Q000502:physiology*; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation / Q000502:physiology
chemical_list: D004271:DNA, Fungal; D004275:DNA, Ribosomal; D018809:Proliferating Cell Nuclear Antigen; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; C061376:SRS2 protein, S cerevisiae; D004265:DNA Helicases
keywords: DNA repair; homologous recombination; proliferating cell nuclear antigen (PCNA); protein-protein interaction; small ubiquitin-like modifier (SUMO)