Pot1 promotes telomere DNA replication via the Stn1-Ten1 complex in fission yeast

Nucleic Acids Res. 2023 Dec 11;51(22):12325-12336. doi: 10.1093/nar/gkad1036.

Abstract

Telomeres are nucleoprotein complexes that protect the chromosome-ends from eliciting DNA repair while ensuring their complete duplication. Pot1 is a subunit of telomere capping complex that binds to the G-rich overhang and inhibits the activation of DNA damage checkpoints. In this study, we explore new functions of fission yeast Pot1 by using a pot1-1 temperature sensitive mutant. We show that pot1 inactivation impairs telomere DNA replication resulting in the accumulation of ssDNA leading to the complete loss of telomeric DNA. Recruitment of Stn1 to telomeres, an auxiliary factor of DNA lagging strand synthesis, is reduced in pot1-1 mutants and overexpression of Stn1 rescues loss of telomeres and cell viability at restrictive temperature. We propose that Pot1 plays a crucial function in telomere DNA replication by recruiting Stn1-Ten1 and Polα-primase complex to telomeres via Tpz1, thus promoting lagging-strand DNA synthesis at stalled replication forks.

MeSH terms

  • Chromosomes, Fungal* / metabolism
  • DNA Replication*
  • DNA-Binding Proteins / metabolism
  • Schizosaccharomyces pombe Proteins* / metabolism
  • Schizosaccharomyces* / metabolism
  • Shelterin Complex
  • Telomere* / metabolism
  • Telomere-Binding Proteins / metabolism

Substances

  • DNA-Binding Proteins
  • pot1 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Shelterin Complex
  • Stn1 protein, S pombe
  • Telomere-Binding Proteins
  • Ten1 protein, S pombe
  • Tpz1 protein, S pombe