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

Author

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  • Wezley C. Griffin

    (Baylor University
    St. Jude Children’s Research Hospital)

  • David R. McKinzey

    (Baylor University)

  • Kathleen N. Klinzing

    (Baylor University)

  • Rithvik Baratam

    (Baylor University)

  • Achini Eliyapura

    (Baylor University)

  • Michael A. Trakselis

    (Baylor University)

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.

Suggested Citation

  • Wezley C. Griffin & David R. McKinzey & Kathleen N. Klinzing & Rithvik Baratam & Achini Eliyapura & Michael A. Trakselis, 2022. "A multi-functional role for the MCM8/9 helicase complex in maintaining fork integrity during replication stress," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32583-8
    DOI: 10.1038/s41467-022-32583-8
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    2. Xianning Lai & Ronan Broderick & Valérie Bergoglio & Jutta Zimmer & Sophie Badie & Wojciech Niedzwiedz & Jean-Sébastien Hoffmann & Madalena Tarsounas, 2017. "Correction: Corrigendum: MUS81 nuclease activity is essential for replication stress tolerance and chromosome segregation in BRCA2-deficient cells," Nature Communications, Nature, vol. 8(1), pages 1-3, December.
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