MAP kinase‐mediated regulation of DNA replication origin licensing and Cdt1 stability

TL;DRAbstract

Eukaryotic cells employ many mechanisms to ensure that their genomes are completely duplicated precisely once each cell cycle. One of the most important of these mechanisms is the regulation of origin licensing by the chromatin loading of the MCM complex through the concerted action of ORC, Cdc6 and Cdt1. Origin licensing control must be maintained even when cells are challenged with extracellular perturbations such as DNA damage or agents that trigger a cellular stress response. We have investigated effects on the origin licensing system mediated by the cellular stress response which is induced by a variety of insults such as hyperosmotic shock, exposure to bacterial toxin, or inflammatory cytokines. Unlike the effects of DNA damage, both Cdt1 and Cdc6 are stable during a cellular stress response; in fact Cdt1 is hyperstable and is no longer a substrate for DNA damage‐induced degradation. Instead, Cdt1 is robustly phosphorylated by the stress‐activated p38 and JNK members of the MAP k

Chat with Paper

AI Agents for this Paper