Work

CRL2Lrr1 promotes unloading of the vertebrate replisome from chromatin during replication termination

Year: 2017

Type: preprint

Abstract: A key event during eukaryotic replication termination is the removal of the CMG helicase from chromatin. CMG unloading involves ubiquitylation of its Mcm7 subunit and the action of the p97 ATPase. Using a proteomic screen in Xenopus egg extracts, we identified factors that are enriched on chromatin when CMG unloading is blocked. This approach identified the E3 ubiquitin ligase CRL2Lrr1, a specific p97 complex, other potential regulators of termination, and many replisome components. We show that Mcm7 ubiquitylation and CRL2Lrr1 binding to chromatin are temporally linked and occur only during replication termination. In the absence of CRL2Lrr1, Mcm7 is not ubiquitylated, CMG unloading is inhibited, and a large subcomplex of the vertebrate replisome that includes DNA Pol ε is retained on DNA. Our data identify CRL2Lrr1 as a master regulator of replisome disassembly during vertebrate DNA replication termination.

Source: Genes & Development

DOI: 10.1101/gad.291799.116

Authors: James M. Dewar, Emily Low, Matthias Mann, Markus Räschle, Johannes C. Walter

Institutions: Harvard University, Max Planck Institute of Biochemistry, Howard Hughes Medical Institute

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Funders: Howard Hughes Medical Institute, National Institutes of Health, National Institute of General Medical Sciences

Award: The mechanism of vertebrate DNA replication termination