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


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.

SUBMITTER: Ogawa S 

PROVIDER: S-EPMC6068461 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Ogawa Shiho S   Kido Sayuri S   Handa Tetsuya T   Ogawa Hidesato H   Asakawa Haruhiko H   Takahashi Tatsuro S TS   Nakagawa Takuro T   Hiraoka Yasushi Y   Masukata Hisao H  

The EMBO journal 20180711 15


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 <i>Schizosaccharomyces pombe</i>, 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 <i>lacO</i>/LacI-  ...[more]

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