Myc-driven chromatin accessibility regulates Cdc45 assembly into CMG helicases.

ABSTRACT: Myc-driven tumorigenesis involves a non-transcriptional role for Myc in over-activating replication origins. We show here that the mechanism underlying this process involves a direct role for Myc in activation of Cdc45-MCM-GINS (CMG) helicases at Myc-targeted sites. Myc induces decondensation of higher-order chromatin at targeted sites and is required for chromatin access at a chromosomal origin. Myc-driven chromatin accessibility promotes Cdc45/GINS recruitment to resident MCMs, and activation of CMGs. Myc-Box II, which is necessary for Myc-driven transformation, is required for Myc-induced chromatin accessibility, Cdc45/GINS recruitment, and replication stimulation. Myc interactors GCN5, Tip60, and TRRAP are essential for chromatin unfolding and recruitment of Cdc45, and co-expression of

SUBMITTER: Nepon-Sixt BS 

PROVIDER: S-EPMC6430796 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature