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

Shiho Ogawa, Sayuri Kido, Tetsuya Handa, Hidesato Ogawa, Haruhiko Asakawa, Tatsuro S. Takahashi, Takuro Nakagawa, Yasushi Hiraoka, Hisao Masukata

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8 Citations (Scopus)

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.

Original languageEnglish
Article numbere98997
JournalEMBO Journal
Volume37
Issue number15
DOIs
Publication statusPublished - Aug 1 2018

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Ogawa, S., Kido, S., Handa, T., Ogawa, H., Asakawa, H., Takahashi, T. S., Nakagawa, T., Hiraoka, Y., & Masukata, H. (2018). Shelterin promotes tethering of late replication origins to telomeres for replication-timing control. EMBO Journal, 37(15), [e98997]. https://doi.org/10.15252/embj.201898997