Distinct SUMO ligases cooperate with Esc2 and Slx5 to suppress duplication-mediated genome rearrangements.
Suppression of duplication-mediated gross chromosomal rearrangements (GCRs) is essential to maintain genome integrity in eukaryotes. Here we report that SUMO ligase Mms21 has a strong role in suppressing GCRs in Saccharomyces cerevisiae, while Siz1 and Siz2 have weaker and partially redundant roles. Understanding the functions of these enzymes has been hampered by a paucity of knowledge of their substrate specificity in vivo. Using a new quantitative SUMO-proteomics technology, we found that Siz1 and Siz2 redundantly control the abundances of most sumoylated substrates, while Mms21 more specifically regulates sumoylation of RNA polymerase-I and the SMC-family proteins. Interestingly, Esc2, a SUMO-like domain-containing protein, specifically promotes the accumulation of sumoylated Mms21-specific substrates and functions with Mms21 to suppress GCRs. On the other hand, the Slx5-Slx8 complex, a SUMO-targeted ubiquitin ligase, suppresses the accumulation of sumoylated Mms21-specific substrates. Thus, distinct SUMO ligases work in concert with Esc2 and Slx5-Slx8 to control substrate specificity and sumoylation homeostasis to prevent GCRs.
Ludwig Institute for Cancer Research, University of California School of Medicine, San Diego, La Jolla, CA, USA.
Claudio P
CP
Albuquerque
Guoliang
G
Wang
Nancy S
NS
Lee
Richard D
RD
Kolodner
Christopher D
CD
Putnam
Huilin
H
Zhou
D018797:Cell Cycle Proteins; D020440:Gene Duplication; D016681:Genome, Fungal; D042822:Genomic Instability; D008025:Ligases / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D013379:Substrate Specificity; D058207:Sumoylation / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
D018797:Cell Cycle Proteins; C532918:Esc2 protein, S cerevisiae; C500948:Mms21 protein, S cerevisiae; D009687:Nuclear Proteins; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; C436836:Siz2 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; C436837:Siz1 protein, S cerevisiae; C515573:Slx5 protein, S cerevisiae