AI Article Synopsis

  • SUMO ligase Mms21 plays a crucial role in preventing gross chromosomal rearrangements (GCRs) in yeast, while Siz1 and Siz2 have weaker, overlapping functions.
  • A new quantitative SUMO-proteomics technology revealed that Mms21 specifically regulates the sumoylation of RNA polymerase-I and SMC-family proteins, whereas Siz1 and Siz2 control the levels of many sumoylated substrates.
  • The protein Esc2 enhances the accumulation of Mms21-specific sumoylated substrates, working alongside Mms21, while the Slx5-Slx8 complex helps reduce these substrates, highlighting the intricate balance of SUMO ligases in maintaining genome integrity.

Article Abstract

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731205PMC
http://dx.doi.org/10.1371/journal.pgen.1003670DOI Listing

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