Control of telomere length in yeast by SUMOylated PCNA and the Elg1 PCNA unloader

Elife. 2023 Aug 2:12:RP86990. doi: 10.7554/eLife.86990.

Abstract

Telomeres cap and protect the linear eukaryotic chromosomes. Telomere length is determined by an equilibrium between positive and negative regulators of telomerase activity. A systematic screen for yeast mutants that affect telomere length maintenance in the yeast Saccharomyces cerevisiae revealed that mutations in any of ~500 genes affects telomere length. One of the genes that, when mutated, causes telomere elongation is ELG1, which encodes an unloader of PCNA, the processivity factor for replicative DNA polymerases. PCNA can undergo SUMOylation on two conserved residues, K164 and K127, or ubiquitination at lysine 164. These modifications have already been implicated in genome stability processes. We report that SUMOylated PCNA acts as a signal that positively regulates telomerase activity. We also uncovered physical interactions between Elg1 and the CST (Cdc13-Stn1-Ten) complex and addressed the mechanism by which Elg1 and Stn1 negatively regulates telomere elongation, coordinated by SUMO. We discuss these results with respect to how chromosomal replication and telomere elongation are coordinated.

Keywords: CST; Cdc13; DNA replication; S. cerevisiae; Stn1; Ten1; chromosomes; gene expression; genetics; genomics; telomere length.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / metabolism
  • Proliferating Cell Nuclear Antigen / genetics
  • Protein Binding
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Telomerase* / metabolism
  • Telomere / metabolism
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism

Substances

  • Proliferating Cell Nuclear Antigen
  • Telomerase
  • Telomere-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • Cdc13 protein, S cerevisiae
  • Elg1 protein, S cerevisiae
  • Carrier Proteins

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.