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

Genes Dev. 2012 Sep 15;26(18):2050-62. doi: 10.1101/gad.194282.112.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA Replication / physiology*
  • DNA, Fungal / genetics
  • DNA, Fungal / metabolism
  • DNA-Binding Proteins / metabolism
  • Molecular Sequence Data
  • Protein Binding
  • Protein Transport
  • Replication Origin / physiology
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces / physiology*
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism*

Substances

  • DNA, Fungal
  • DNA-Binding Proteins
  • Schizosaccharomyces pombe Proteins
  • Sld3 protein, S pombe
  • Telomere-Binding Proteins
  • taz1 protein, S pombe