Telomere length regulation by Rif1 protein from Hansenula polymorpha

eLife

Vladimir I Polshakov¹  Olga A Petrova²  Alexander N Malyavko²  Maria I Zvereva²  Olga A Dontsova³ 

[1] Center for Magnetic Tomography and Spectroscopy, Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow, Russian Federation;Faculty of Chemistry and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russian Federation;Faculty of Chemistry and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russian Federation;Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation;Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russian Federation;

关键词: telomere;    telomerase;    Hansenula polymorpha;    genome stability;    DNA replication;    Rif1;    Other;   

DOI  :  10.7554/eLife.75010

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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 Hansenula polymorpha DL-1. We show that, similar to other yeast species, H. polymorpha Rif1 suppresses telomerase-dependent telomere elongation. We uncover two novel modes of Rif1 recruitment at H. polymorpha 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 H. polymorpha.

【 授权许可】

CC BY