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Reference - PMID:29997179 - Shelterin promotes tethering of late replication origins to telomeres for replication-timing control.

Reference summary

PubMed ID
PMID:29997179
Title
Shelterin promotes tethering of late replication origins to telomeres for replication-timing control.
Authors
Ogawa S, Kido S, Handa T, Ogawa H, Asakawa H, Takahashi TS, Nakagawa T, Hiraoka Y, Masukata H
Citation
EMBO J 2018 Aug 01;37(15)
Publication year
2018
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.

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