MCM7 Ubiquitination Regulates CMG Helicase Disassembly In Human

Abstract

The disassembly of the replisome plays an essential role in maintaining genome stability at the termination of DNA replication. However, the mechanism of replisome disassembly remains unknown in human. In this study, we screened E3 ligases and deubiquitinases (DUBs) for the ubiquitination of minichromosome maintenance protein (MCM) 7 and provided evidence of this process driving CMG helicase disassembly in human tumor cells. Our data identified two important features of helicase disassembly in human. First, RNF8 catalyzes the K63-linkedpolyubiquitylation of MCM7 on chromatin, which is transiently modified mainly in the late S phase of the cell cycle. Moreover, the proteasome, p97 segregase, USP29 and ATXN3 are required for the removal of MCM7 ubiquitination to promote the disassembly of CMG on chromatin. Our study will help to uncover the novel role of the regulation of CMG helicase disassembly via MCM7 ubiquitination.