A DNA damage-induced phosphorylation circuit enhances Mec1^ATR Ddc2^ATRIP recruitment to Replication Protein A.

ABSTRACT: The cell cycle checkpoint kinase Mec1^ATR and its integral partner Ddc2^ATRIP are vital for the DNA damage and replication stress response. Mec1-Ddc2 "senses" single-stranded DNA (ssDNA) by being recruited to the ssDNA binding Replication Protein A (RPA) via Ddc2. In this study, we show that a DNA damage-induced phosphorylation circuit modulates checkpoint recruitment and function. We demonstrate that Ddc2-RPA interactions modulate the association between RPA and ssDNA and that Rfa1-phosphorylation aids in the further recruitment of Mec1-Ddc2. We also uncover an underappreciated role for Ddc2 phosphorylation that enhances its recruitment to RPA-ssDNA that is important for the DNA damage checkpoint in yeast. The crystal structure of a phosphorylated Ddc2 peptide in compl

SUBMITTER: Yates LA 

PROVIDER: S-EPMC10083555 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature