The telomere-binding protein Rif2 and ATP-bound Rad50 have opposing roles in the activation of yeast Tel1^ATM kinase.

ABSTRACT: Saccharomyces cerevisiae Tel1 is the ortholog of human ATM kinase and initiates a cell cycle checkpoint in response to dsDNA breaks (DSBs). Tel1^ATM kinase is activated synergistically by naked dsDNA and the Mre11-Rad50-Xrs2^NBS1 complex (MRX). A multisubunit protein complex, which is related to human shelterin, protects telomeres from being recognized as DSBs, thereby preventing a Tel1^ATM checkpoint response. However, at very short telomeres, Tel1^ATM can be recruited and activated by the MRX complex, resulting in telomere elongation. Conversely, at long telomeres, Rap1-interacting-factor 2 (Rif2) is instrumental in suppressing Tel1 activity. Here, using an in vitro reconstituted Tel1 kinase activation assay, we show that Rif2 inhibit

SUBMITTER: Hailemariam S 

PROVIDER: S-EPMC6901328 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature