CDC7 kinase promotes MRE11 fork processing, modulating fork speed and chromosomal breakage.

ABSTRACT: The CDC7 kinase is essential for the activation of DNA replication origins and has been implicated in the replication stress response. Using a highly specific chemical inhibitor and a chemical genetic approach, we now show that CDC7 activity is required to coordinate multiple MRE11-dependent processes occurring at replication forks, independently from its role in origin firing. CDC7 localizes at replication forks and, similarly to MRE11, mediates active slowing of fork progression upon mild topoisomerase inhibition. Both proteins are also retained on stalled forks, where they promote fork processing and restart. Moreover, MRE11 phosphorylation and localization at replication factories are progressively lost upon CDC7 inhibition. Finally, CDC7 activity at reversed forks is required for thei

SUBMITTER: Rainey MD 

PROVIDER: S-EPMC7403700 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature