Shelterin promotes tethering of late replication origins to telomeres for replication-timing control

EMBO J. 2018 Aug 1;37(15):e98997. doi: 10.15252/embj.201898997. Epub 2018 Jul 11.

Abstract

DNA replication initiates at many discrete loci on eukaryotic chromosomes, and individual replication origins are regulated under a spatiotemporal program. However, the underlying mechanisms of this regulation remain largely unknown. In the fission yeast Schizosaccharomyces pombe, the telomere-binding protein Taz1, ortholog of human TRF1/TRF2, regulates a subset of late replication origins by binding to the telomere-like sequence near the origins. Here, we showed using a lacO/LacI-GFP system that Taz1-dependent late origins were predominantly localized at the nuclear periphery throughout interphase, and were localized adjacent to the telomeres in the G1/S phase. The peripheral localization that depended on the nuclear membrane protein Bqt4 was not necessary for telomeric association and replication-timing control of the replication origins. Interestingly, the shelterin components Rap1 and Poz1 were required for replication-timing control and telomeric association of Taz1-dependent late origins, and this requirement was bypassed by a minishelterin Tpz1-Taz1 fusion protein. Our results suggest that Taz1 suppresses replication initiation through shelterin-mediated telomeric association of the origins at the onset of S phase.

Keywords: Rap1; Taz1; chromatin organization; replication timing; telomere.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Replication / genetics
  • DNA-Binding Proteins / metabolism
  • G1 Phase / genetics
  • Membrane Proteins / metabolism
  • Nuclear Proteins / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Replication Origin / genetics*
  • S Phase / genetics
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Telomere / metabolism*
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism*
  • Telomeric Repeat Binding Protein 2 / metabolism*

Substances

  • Bqt4 protein, S pombe
  • DNA-Binding Proteins
  • Membrane Proteins
  • Nuclear Proteins
  • Poz1 protein, S pombe
  • Rap1 protein, S pombe
  • Recombinant Fusion Proteins
  • Schizosaccharomyces pombe Proteins
  • Telomere-Binding Proteins
  • Telomeric Repeat Binding Protein 2
  • taz1 protein, S pombe