Mec1^ATR Autophosphorylation and Ddc2^ATRIP Phosphorylation Regulates DNA Damage Checkpoint Signaling.

ABSTRACT: In budding yeast, a single DNA double-strand break (DSB) triggers the activation of Mec1^ATR-dependent DNA damage checkpoint. After about 12 h, cells turn off the checkpoint signaling and adapt despite the persistence of the DSB. We report that the adaptation involves the autophosphorylation of Mec1 at site S1964. A non-phosphorylatable mec1-S1964A mutant causes cells to arrest permanently in response to a single DSB without affecting the initial kinase activity of Mec1. Autophosphorylation of S1964 is dependent on Ddc1^Rad9 and Dpb11^TopBP1, and it correlates with the timing of adaptation. We also report that Mec1's binding partner, Ddc2^ATRIP, is an inherently stable protein that is degraded specifically upon DNA damage. Ddc2 is regulated extensive

SUBMITTER: Memisoglu G 

PROVIDER: S-EPMC7218798 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature