Telomere-binding factors in the regulation of DNA replication

Abstract

Recent studies have indicated new roles for telomere-binding factors in the regulation of DNA replication, not only at the telomeres but also at the arm regions of the chromosome. Among these factors, Rif1, a conserved protein originally identified in yeasts as a telomere regulator, plays a major role in the spatiotemporal regulation of DNA replication during S phase. Its ability to interact with phosphatases and to create specific higher-order chromatin structures is central to the mechanism by which Rif1 exerts this function. In this review, we discuss recent progress in elucidating the roles of Rif1 and other telomere-binding factors in the regulation of chromosome events occurring at locations other than telomeres.

Rif1 promotes association of G-quadruplex (G4) by its specific G4 binding and oligomerization activities

“…In yeasts, Rif1 not only binds to telomere but also to selected segments on the chromosome arms 6,47,48 . Genome-wide analyses of Rif1 binding sites and subsequent analyses of the binding sequences revealed the presence of a conserved G-rich sequence 31 .…”

The fission yeast Stn1-Ten1 complex limits telomerase activity via its SUMO-interacting motif and promotes telomeres replication

“…One interesting observation is that stn1-226 defects are fully complemented by the deletion of rif1 + . Rif1 is a multifaceted protein that is involved in fission yeast in telomerase inhibition, in cytokinesis, and in the timing of the replication at a high temperature ( 49 ). In budding yeast, ScRif1 also exhibits a DNA repair function as the human RIF1 ( 50 , 51 ).…”

RIF1 Links Replication Timing with Fork Reactivation and DNA Double-Strand Break Repair

“…Human RIF1 has BLM interacting domain, which supports recruiting the BLM helicase to stalled replication fork. Structural features of RIF1 and its ability to oligomerize underline its preferential binding to G4-quadruplexes (G4s) DNA, a four-stranded DNA resulting from the ability of guanine bases to form stable hydrogen bonds with other guanines [ 27 , 28 ]. In human cells, RIF1 localizes at nuclease-insoluble structures at the nuclear membranes and the periphery of the nucleoli.…”