title: Smc5/6 Mediated Sumoylation of the Sgs1-Top3-Rmi1 Complex Promotes Removal of Recombination Intermediates.
abstract: Timely removal of DNA recombination intermediates is critical for genome stability. The DNA helicase-topoisomerase complex, Sgs1-Top3-Rmi1 (STR), is the major pathway for processing these intermediates to generate conservative products. However, the mechanisms that promote STR-mediated functions remain to be defined. Here we show that Sgs1 binds to poly-SUMO chains and associates with the Smc5/6 SUMO E3 complex in yeast. Moreover, these interactions contribute to the sumoylation of Sgs1, Top3, and Rmi1 upon the generation of recombination structures. We show that reduced STR sumoylation leads to accumulation of recombination structures, and impaired growth in conditions when these structures arise frequently, highlighting the importance of STR sumoylation. Mechanistically, sumoylation promotes STR inter-subunit interactions and accumulation at DNA repair centers. These findings expand the roles of sumoylation and Smc5/6 in genome maintenance by demonstrating that they foster STR functions in the removal of recombination intermediates.
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Programs in Biochemistry, Cell, and Molecular Biology, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.
authors.forename: Jacob N
authors.initials: JN
authors.lastname: Bonner
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Programs in Biochemistry, Cell, and Molecular Biology, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.
authors.forename: Koyi
authors.initials: K
authors.lastname: Choi
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Xue
authors.affiliation: Donnelly Centre and Department of Biochemistry, University of Toronto, Toronto, ON M5S 3E1, Canada.
authors.forename: Nikko P
authors.initials: NP
authors.lastname: Torres
authors.affiliation: IFOM, The FIRC of Molecular Oncology, Via Adamello 16, 20139, Milan, Italy.
authors.forename: Barnabas
authors.initials: B
authors.lastname: Szakal
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Wei
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Wan
authors.affiliation: Institute of Biochemistry, Swiss Federal Institute of Technology in Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.
authors.forename: Meret
authors.initials: M
authors.lastname: Arter
authors.affiliation: Institute of Biochemistry, Swiss Federal Institute of Technology in Zürich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland.
authors.forename: Joao
authors.initials: J
authors.lastname: Matos
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Sung
authors.affiliation: Donnelly Centre and Department of Biochemistry, University of Toronto, Toronto, ON M5S 3E1, Canada.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Brown
authors.affiliation: IFOM, The FIRC of Molecular Oncology, Via Adamello 16, 20139, Milan, Italy.
authors.forename: Dana
authors.initials: D
authors.lastname: Branzei
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Programs in Biochemistry, Cell, and Molecular Biology, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA. Electronic address: zhaox1@mskcc.org.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000502:physiology; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D053484:RecQ Helicases / Q000378:metabolism*; D011995:Recombination, Genetic; D025842:SUMO-1 Protein / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology; D058207:Sumoylation; D020798:Two-Hybrid System Techniques
chemical_list: D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C500948:Mms21 protein, S cerevisiae; C502206:Rmi1 protein, S cerevisiae; C486627:SMC5 protein, S cerevisiae; C486631:SMC6 protein, S cerevisiae; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; C502374:TOP3 protein, S cerevisiae; C090472:SGS1 protein, S cerevisiae; D053484:RecQ Helicases
keywords: Sgs1; Smc5/6; protein sumoylation; recombination intermediates