Activation of Tel1^ATM kinase requires Rad50 ATPase and long nucleosome-free DNA but no DNA ends.

ABSTRACT: In Saccharomyces cerevisiae, Tel1 protein kinase, the ortholog of human ataxia telangiectasia-mutated (ATM), is activated in response to DNA double-strand breaks. Biochemical studies with human ATM and genetic studies in yeast suggest that recruitment and activation of Tel1^ATM depends on the heterotrimeric MRX^MRN complex, composed of Mre11, Rad50, and Xrs2 (human Nbs1). However, the mechanism of activation of Tel1 by MRX remains unclear, as does the role of effector DNA. Here we demonstrate that dsDNA and MRX activate Tel1 synergistically. Although minimal activation was observed with 80-mer duplex DNA, the optimal effector for Tel1 activation is long, nucleosome-free DNA. However, there is no requirement for DNA double-stranded termini. The ATPase activity of

SUBMITTER: Hailemariam S 

PROVIDER: S-EPMC6664182 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature