A multi-functional role for the MCM8/9 helicase complex in maintaining fork integrity during replication stress.

ABSTRACT: The minichromosome maintenance (MCM) 8/9 helicase is a AAA⁺ complex involved in DNA replication-associated repair. Despite high sequence homology to the MCM2-7 helicase, a precise cellular role for MCM8/9 has remained elusive. We have interrogated the DNA synthesis ability and replication fork stability in cells lacking MCM8 or 9 and find that there is a functional partitioning of MCM8/9 activity between promoting replication fork progression and protecting persistently stalled forks. The helicase function of MCM8/9 aids in normal replication fork progression, but upon persistent stalling, MCM8/9 directs additional downstream stabilizers, including BRCA1 and Rad51, to protect forks from excessive degradation. Loss of MCM8 or 9 slows the overall replication rate and allows for ex

SUBMITTER: Griffin WC 

PROVIDER: S-EPMC9427862 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature