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Shelterin promotes tethering of late replication origins to telomeres for replication‐timing control
Author(s) -
Ogawa Shiho,
Kido Sayuri,
Handa Tetsuya,
Ogawa Hidesato,
Asakawa Haruhiko,
Takahashi Tatsuro S,
Nakagawa Takuro,
Hiraoka Yasushi,
Masukata Hisao
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201898997
Subject(s) - frontier , graduate students , library science , biology , history , medicine , medical education , computer science , archaeology
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 TRF 1/ TRF 2, 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.