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

In eukaryotes, 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 these 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 fragment 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 copies of a telomeric repeat are essential for this repression. The telomeric repeats recruit Taz1, a fission yeast counterpart of human TRF1/2, to the locus. Genome-wide analysis revealed that Taz1 regulates about half of all chromosomal late origins, including those in sub-telomeres. A step of DDK-dependent Sld3 loading onto the origin is prevented by a Taz1-mediated mechanism. Our results demonstrate that the replication-timing program in fission yeast utilizes the internal telomeric repeats and binding of Taz1.