End-joining inhibition at telomeres requires the translocase and polySUMO-dependent ubiquitin ligase Uls1

Rachel Lescasse; Sabrina Pobiega; Isabelle Callebaut; Stéphane Marcand

doi:10.1038/emboj.2013.24

End-joining inhibition at telomeres requires the translocase and polySUMO-dependent ubiquitin ligase Uls1

EMBO J. 2013 Mar 20;32(6):805-15. doi: 10.1038/emboj.2013.24. Epub 2013 Feb 15.

Authors

Rachel Lescasse¹, Sabrina Pobiega, Isabelle Callebaut, Stéphane Marcand

Affiliation

¹ CEA, Direction des sciences du vivant/Institut de radiobiologie cellulaire et moléculaire/Service instabilité génétique réparation recombinaison/Laboratoire télomère et réparation du chromosome, Fontenay-aux-roses, France.

Abstract

In eukaryotes, permanent inhibition of the non-homologous end joining (NHEJ) repair pathway at telomeres ensures that chromosome ends do not fuse. In budding yeast, binding of Rap1 to telomere repeats establishes NHEJ inhibition. Here, we show that the Uls1 protein is required for the maintenance of NHEJ inhibition at telomeres. Uls1 protein is a non-essential Swi2/Snf2-related translocase and a Small Ubiquitin-related Modifier (SUMO)-Targeted Ubiquitin Ligase (STUbL) with unknown targets. Loss of Uls1 results in telomere-telomere fusions. Uls1 requirement is alleviated by the absence of poly-SUMO chains and by rap1 alleles lacking SUMOylation sites. Furthermore, Uls1 limits the accumulation of Rap1 poly-SUMO conjugates. We propose that one of Uls1 functions is to clear non-functional poly-SUMOylated Rap1 molecules from telomeres to ensure the continuous efficiency of NHEJ inhibition. Since Uls1 is the only known STUbL with a translocase activity, it can be the general molecular sweeper for the clearance of poly-SUMOylated proteins on DNA in eukaryotes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA End-Joining Repair*
DNA Helicases / metabolism
DNA Helicases / physiology*
Down-Regulation
Organisms, Genetically Modified
Peptidyl Transferases / metabolism
Peptidyl Transferases / physiology
Protein Binding
Protein Multimerization / physiology
SUMO-1 Protein / metabolism
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / metabolism
Saccharomyces cerevisiae Proteins / physiology*
Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism
Silent Information Regulator Proteins, Saccharomyces cerevisiae / physiology
Small Ubiquitin-Related Modifier Proteins / metabolism
Small Ubiquitin-Related Modifier Proteins / physiology
Sumoylation / physiology
Telomere / metabolism*
Ubiquitin-Protein Ligases / metabolism
Ubiquitin-Protein Ligases / physiology
rap1 GTP-Binding Proteins / metabolism

Substances

SIR4 protein, S cerevisiae
SMT3 protein, S cerevisiae
SUMO-1 Protein
Saccharomyces cerevisiae Proteins
Silent Information Regulator Proteins, Saccharomyces cerevisiae
Small Ubiquitin-Related Modifier Proteins
Peptidyl Transferases
Ubiquitin-Protein Ligases
ULS1 protein, S cerevisiae
DNA Helicases
rap1 GTP-Binding Proteins