Telomere length regulation by Rif1 protein from <i>Hansenula polymorpha</i>.

Abstract

Rif1 is a large multifaceted protein involved in various processes of DNA metabolism - from telomere length regulation and replication to double-strand break repair. The mechanistic details of its action, however, are often poorly understood. Here, we report functional characterization of the Rif1 homologue from methylotrophic thermotolerant budding yeast <i>Hansenula polymorpha</i> DL-1. We show that, similar to other yeast species, <i>H. polymorpha</i> Rif1 suppresses telomerase-dependent telomere elongation. We uncover two novel modes of Rif1 recruitment at <i>H. polymorpha</i> telomeres: via direct DNA binding and through the association with the Ku heterodimer. Both of these modes (at least partially) require the intrinsically disordered N-terminal extension - a region of the protein present exclusively in yeast species. We also demonstrate that Rif1 binds Stn1 and promotes its accumulation at telomeres in <i>H. polymorpha</i>.