Minichromosome Maintenance 8 Homologous Recombination Repair Factor (MCM8) and Minichromosome Maintenance 9 Homologous Recombination Repair Factor (MCM9) are recently discovered minichromosome maintenance proteins and are implicated in multiple DNA-related processes and pathologies, including DNA replication (initiation), meiosis, homologous recombination and mismatch repair. Consistent with these molecular functions, variants of may predispose carriers to disorders such as infertility and cancer and should therefore be included in relevant diagnostic testing. In this overview of the (patho)physiological functions of MCM8 and MCM9 and the phenotype of variant carriers, we explore the potential clinical implications of variant carriership and highlight important future directions of MCM8 and MCM9 research. With this review, we hope to contribute to better variant carrier management and the potential utilization of MCM8 and MCM9 in other facets of scientific research and medical care.
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http://dx.doi.org/10.1016/j.isci.2023.106737 | DOI Listing |
Nat Cardiovasc Res
August 2023
Clinical Biological Resource Bank and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Mitophagy is a major quality control pathway that removes unwanted or dysfunctional mitochondria and plays an essential role in vascular health. Here we show that MCM8 expression is significantly decreased in children with Kawasaki disease (KD) who developed coronary artery aneurysms. Mechanistically, we discovered that nitric oxide signaling promotes TRIM21-mediated MCM8 ubiquitination, which disrupts its interaction with MCM9 and promotes its cytosolic export.
View Article and Find Full Text PDFNat Commun
April 2024
Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Bellinzona, 6500, Switzerland.
HROB promotes the MCM8-9 helicase in DNA damage response. To understand how HROB activates MCM8-9, we defined their interaction interface. We showed that HROB makes important yet transient contacts with both MCM8 and MCM9, and binds the MCM8-9 heterodimer with the highest affinity.
View Article and Find Full Text PDFElife
August 2023
Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
MCM8 and MCM9 form a functional helicase complex (MCM8/9) that plays an essential role in DNA homologous recombination repair for DNA double-strand break. However, the structural characterization of MCM8/9 for DNA binding/unwinding remains unclear. Here, we report structures of the MCM8/9 complex using cryo-electron microscopy single particle analysis.
View Article and Find Full Text PDFRes Sq
June 2023
Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Bellinzona, 6500, Switzerland.
The human MCM8-9 helicase functions in concert with HROB in the context of homologous recombination, but its precise function is unknown. To gain insights into how HROB regulates MCM8-9, we first used molecular modeling and biochemistry to define their interaction interface. We show that HROB makes important contacts with both MCM8 and MCM9 subunits, which directly promotes its DNA-dependent ATPase and helicase activities.
View Article and Find Full Text PDFThe human MCM8-9 helicase functions in concert with HROB in the context of homologous recombination, but its precise function is unknown. To gain insights into how HROB regulates MCM8-9, we first used molecular modeling and biochemistry to define their interaction interface. We show that HROB makes important contacts with both MCM8 and MCM9 subunits, which directly promotes its DNA-dependent ATPase and helicase activities.
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