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A multi-functional role for the MCM8/9 helicase complex in maintaining fork integrity during replication stress. 2022

Wezley C Griffin, and David R McKinzey, and Kathleen N Klinzing, and Rithvik Baratam, and Achini Eliyapura, and Michael A Trakselis
Department of Chemistry and Biochemistry, Baylor University, Waco, TX, 76706, USA.

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.

UI MeSH Term Description Entries
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D004261 DNA Replication The process by which a DNA molecule is duplicated. Autonomous Replication,Replication, Autonomous,Autonomous Replications,DNA Replications,Replication, DNA,Replications, Autonomous,Replications, DNA
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D042822 Genomic Instability An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional. Genome Instability,Genome Stability,Genomic Stability,Genome Instabilities,Genome Stabilities,Genomic Instabilities,Genomic Stabilities,Instabilities, Genome,Instabilities, Genomic,Instability, Genome,Instability, Genomic,Stabilities, Genome,Stabilities, Genomic,Stability, Genome,Stability, Genomic
D064110 Minichromosome Maintenance Proteins A family of proteins that were originally identified in SACCHAROMYCES CEREVISIAE as being essential for maintaining the structure of minichromosomes00. They form into a protein complex that has helicase activity and is involved in a variety of DNA-related functions including replication elongation, RNA transcription, chromatin remodeling, and genome stability. MCM Protein Complex,MCM2-7 Complex,MCM2-7 Helicase,Helicase, MCM2-7,MCM2 7 Complex,MCM2 7 Helicase,Maintenance Proteins, Minichromosome

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