| Literature DB >> 25752575 |
Francisco Meirelles Bastos de Oliveira1, Dongsung Kim1, José Renato Cussiol1, Jishnu Das2, Min Cheol Jeong2, Lillian Doerfler3, Kristina Hildegard Schmidt4, Haiyuan Yu2, Marcus Bustamante Smolka5.
Abstract
The Mec1/Tel1 kinases (human ATR/ATM) play numerous roles in the DNA replication stress response. Despite the multi-functionality of these kinases, studies of their in vivo action have mostly relied on a few well-established substrates. Here we employed a combined genetic-phosphoproteomic approach to monitor Mec1/Tel1 signaling in a systematic, unbiased, and quantitative manner. Unexpectedly, we find that Mec1 is highly active during normal DNA replication, at levels comparable or higher than Mec1's activation state induced by replication stress. This "replication-correlated" mode of Mec1 action requires the 9-1-1 clamp and the Dna2 lagging-strand factor and is distinguishable from Mec1's action in activating the downstream kinase Rad53. We propose that Mec1/ATR performs key functions during ongoing DNA synthesis that are distinct from their canonical checkpoint role during replication stress.Entities:
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Year: 2015 PMID： 25752575 PMCID： PMC4369404 DOI： 10.1016/j.molcel.2015.01.043
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970