title: The Smc5-Smc6 complex regulates recombination at centromeric regions and affects kinetochore protein sumoylation during normal growth.
abstract: The Smc5-Smc6 complex in Saccharomyces cerevisiae is both essential for growth and important for coping with genotoxic stress. While it facilitates damage tolerance throughout the genome under genotoxin treatment, its function during unperturbed growth is mainly documented for repetitive DNA sequence maintenance. Here we provide physical and genetic evidence showing that the Smc5-Smc6 complex regulates recombination at non-repetitive loci such as centromeres in the absence of DNA damaging agents. Mutating Smc6 results in the accumulation of recombination intermediates at centromeres and other unique sequences as assayed by 2D gel analysis. In addition, smc6 mutant cells exhibit increased levels of Rad52 foci that co-localize with centromere markers. A rad52 mutation that decreases centromeric, but not overall, levels of Rad52 foci in smc6 mutants suppresses the nocodazole sensitivity of these cells, suggesting that the Smc6-mediated regulation of recombination at centromeric regions impacts centromere-related functions. In addition to influencing recombination, the SUMO ligase subunit of the Smc5-Smc6 complex promotes the sumoylation of two kinetochore proteins and affects mitotic spindles. These results suggest that the Smc5-Smc6 complex regulates both recombination and kinetochore sumoylation to facilitate chromosomal maintenance during growth.
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Yong-Gonzales
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hang
authors.forename: Federica
authors.initials: F
authors.lastname: Castellucci
authors.forename: Dana
authors.initials: D
authors.lastname: Branzei
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhao
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D002503:Centromere / Q000502:physiology*; D015825:Chromosomes, Fungal / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair; D015180:Electrophoresis, Gel, Two-Dimensional; D018386:Kinetochores / 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*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D008941:Spindle Apparatus; D058207:Sumoylation
chemical_list: D018797:Cell Cycle Proteins; C500948:Mms21 protein, S cerevisiae; C486627:SMC5 protein, S cerevisiae; C486631:SMC6 protein, S cerevisiae; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins