Abstract
Telomeres are repetitive nucleoprotein structures that cap the ends of chromosomes. Without telomerase, telomeres shorten with replication and eventually signal cell cycle arrest (cell senescence). Homologous recombination (HR)-based mechanisms slow senescence, and distinct HR mechanisms support the growth of the rare survivors of senescence. Here, we report novel roles for the post-translational modification of small ubiquitin-like modifier (SUMO) in regulating the rate of senescence in Saccharomyces cerevisiae telomerase mutants. We identify Mms21 as the relevant SUMO E3 ligase and demonstrate that cells lacking Mms21-dependent sumoylation accumulate HR intermediates selectively at telomeres during senescence. One target of Mms21-dependent sumoylation is the cohesin- and condensin-related Smc5-Smc6 complex (Smc5/6). We show that hypomorphic smc5 or smc6 alleles exhibit phenotypes similar to mms21 sumoylation-deficient mutants with regard to senescence and the accumulation of unresolved HR intermediates. Further, we provide evidence that Mms21 and Smc5/6 prevent aberrant recombination between sister telomeres and also globally facilitate resolution of sister chromatid HR intermediates.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Cell Cycle Proteins / chemistry
-
Cell Cycle Proteins / genetics*
-
Cell Cycle Proteins / metabolism*
-
Chromosomes, Fungal / genetics
-
Chromosomes, Fungal / metabolism
-
DNA Damage
-
DNA Repair
-
DNA Replication
-
DNA, Fungal / genetics
-
DNA, Fungal / metabolism
-
Genes, Fungal
-
Models, Biological
-
Multiprotein Complexes
-
Mutation
-
Protein Processing, Post-Translational
-
Recombination, Genetic
-
SUMO-1 Protein / genetics
-
SUMO-1 Protein / metabolism
-
Saccharomyces cerevisiae / cytology
-
Saccharomyces cerevisiae / genetics
-
Saccharomyces cerevisiae / metabolism
-
Saccharomyces cerevisiae Proteins / chemistry
-
Saccharomyces cerevisiae Proteins / genetics*
-
Saccharomyces cerevisiae Proteins / metabolism*
-
Small Ubiquitin-Related Modifier Proteins / chemistry
-
Small Ubiquitin-Related Modifier Proteins / genetics
-
Small Ubiquitin-Related Modifier Proteins / metabolism*
-
Telomere / genetics
-
Telomere / metabolism
-
Ubiquitin-Protein Ligases / genetics
-
Ubiquitin-Protein Ligases / metabolism
Substances
-
Cell Cycle Proteins
-
DNA, Fungal
-
Mms21 protein, S cerevisiae
-
Multiprotein Complexes
-
SMC5 protein, S cerevisiae
-
SMC6 protein, S cerevisiae
-
SUMO-1 Protein
-
Saccharomyces cerevisiae Proteins
-
Small Ubiquitin-Related Modifier Proteins
-
Ubiquitin-Protein Ligases