A Multi-functional Role for the MCM8/9 Helicase Complex in Maintaining Fork Integrity During Replication Stress

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Aug 30

PMID 36042199

Authors

Wezley C Griffin

David R McKinzey

Kathleen N Klinzing

Rithvik Baratam

Achini Eliyapura

Michael A Trakselis

Affiliations

Soon will be listed here.

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 excessive nascent strand degradation, detectable by increased markers of genomic damage. This evidence defines multifunctional roles for MCM8/9 in promoting normal replication fork progression and genome integrity following stress.

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