Molecular functions of MCM8 and MCM9 and their associated pathologies
Noah Cornelis Helderman,
Diantha Terlouw,
Laia Bonjoch,
Mariano Golubicki,
Marina Antelo,
Hans Morreau,
Tom van Wezel,
Sergi Castellví-Bel,
Yael Goldberg,
Maartje Nielsen
Affiliations
Noah Cornelis Helderman
Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands
Diantha Terlouw
Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands
Laia Bonjoch
Gastroenterology Department, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
Mariano Golubicki
Oncology Section and Molecular Biology Laboratory, Hospital of Gastroenterology ''Dr. C.B. Udaondo'', Buenos Aires, Argentina
Marina Antelo
Oncology Section and Molecular Biology Laboratory, Hospital of Gastroenterology ''Dr. C.B. Udaondo'', Buenos Aires, Argentina
Hans Morreau
Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands
Tom van Wezel
Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands
Sergi Castellví-Bel
Gastroenterology Department, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
Yael Goldberg
Raphael Recanati Genetic Institute, Rabin Medical Center-Beilinson Hospital, Petah Tikva, Israel
Maartje Nielsen
Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands; Corresponding author
Summary: 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 MCM8/MCM9 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 MCM8/MCM9 variant carriers, we explore the potential clinical implications of MCM8/MCM9 variant carriership and highlight important future directions of MCM8 and MCM9 research. With this review, we hope to contribute to better MCM8/MCM9 variant carrier management and the potential utilization of MCM8 and MCM9 in other facets of scientific research and medical care.
