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

Wezley C. Griffin, David R. McKinzey, Kathleen N. Klinzing, Rithvik Baratam, Achini Eliyapura and Michael A. Trakselis ()
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Wezley C. Griffin: Baylor University
David R. McKinzey: Baylor University
Kathleen N. Klinzing: Baylor University
Rithvik Baratam: Baylor University
Achini Eliyapura: Baylor University
Michael A. Trakselis: Baylor University

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32583-8

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