DNA replication licensing factor MCM8 (MCM8) (MCM8)

DNA replication licensing factor MCM8 (MCM8) is a member of the minichromosome maintenance protein family, which plays a critical role in maintaining genomic integrity [UniProt: Q9UJA3]. Unlike the MCM2-7 complex that acts as the replicative helicase, MCM8 forms a complex with MCM9 to function specifically in DNA double-strand break repair via homologous recombination and the repair of DNA interstrand crosslinks [PMID: 21981920, PMID: 23401855]. It possesses 3' to 5' DNA helicase activity and is recruited to damaged DNA sites through the Fanconi anemia pathway [PMID: 21981920]. Mutations in the MCM8 gene are strongly linked to primary ovarian insufficiency (POI) and hypergonadotropic hypogonadism, as the protein is essential for meiotic progression and the maintenance of the germ cell pool [PMID: 25038751]. In the context of oncology, MCM8 is frequently overexpressed in various cancers, such as ovarian and bladder cancer, where it is associated with poor prognosis and resistance to DNA-damaging chemotherapeutic agents like cisplatin [PMID: 30603347]. Consequently, MCM8 is being investigated as a therapeutic target, where its inhibition—potentially through RNA interference or small-molecule inhibitors—could sensitize tumor cells to treatment [PMID: 30603347].

Other names

Minichromosome maintenance complex component 8RECMCM8L

Inhibition of DNA helicase activity or reduction of mRNA/protein expression to impair DNA repair mechanisms.