Telomere-binding protein Taz1 controls global replication timing through its localization near late replication origins in fission yeast

Atsutoshi Tazumi, Masayoshi Fukuura, Ryuichiro Nakato, Ami Kishimoto, Tomokazu Takenaka, Shiho Ogawa, Ji Hoon Song, Tatsuro S. Takahashi, Takuro Nakagawa, Katsuhiko Shirahige, Hisao Masukata

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

Abstract

In eukaryotes, the replication of chromosome DNA is coordinated by a replication timing program that temporally regulates the firing of individual replication origins. However, the molecular mechanism underlying the program remains elusive. Here, we report that the telomere-binding protein Taz1 plays a crucial role in the control of replication timing in fission yeast. A DNA element located proximal to a late origin in the chromosome arm represses initiation from the origin in early S phase. Systematic deletion and substitution experiments demonstrated that two tandem telomeric repeats are essential for this repression. The telomeric repeats recruit Taz1, a counterpart of human TRF1 and TRF2, to the locus. Genome-wide analysis revealed that Taz1 regulates about half of chromosomal late origins, including those in subtelomeres. The Taz1-mediated mechanism prevents Dbf4-dependent kinase (DDK)-dependent Sld3 loading onto the origins. Our results demonstrate that the replication timing program in fission yeast uses the internal telomeric repeats and binding of Taz1.

Original languageEnglish
Pages (from-to)2050-2062
Number of pages13
JournalGenes and Development
Volume26
Issue number18
DOIs
Publication statusPublished - Sep 15 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

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