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

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

Author information

1
Graduate School of Science, Osaka University, Toyonaka Osaka, Japan.
2
Graduate School of Frontier Biosciences, Osaka University, Suita Osaka, Japan.
3
Graduate School of Science, Osaka University, Toyonaka Osaka, Japan masukata@bio.sci.osaka-u.ac.jp.

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

PMID:
29997179
PMCID:
PMC6068461
DOI:
10.15252/embj.201898997
[Indexed for MEDLINE]
Free PMC Article

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