Ask about this productRelated genes to: MCM8 Blocking Peptide
- Gene:
- MCM8 NIH gene
- Name:
- minichromosome maintenance 8 homologous recombination repair factor
- Previous symbol:
- C20orf154
- Synonyms:
- MGC4816, MGC12866, MGC119522, MGC119523, dJ967N21.5, REC
- Chromosome:
- 20p12.3
- Locus Type:
- gene with protein product
- Date approved:
- 2001-07-17
- Date modifiied:
- 2015-08-25
Related products to: MCM8 Blocking Peptide
Related articles to: MCM8 Blocking Peptide
- The minichromosomal maintenance MCM8 and MCM9 proteins form a heterohexameric complex that acts to unwind or remodel duplex DNA in DNA recombination and repair pathways. Mutations or absence of MCM8/9 have been linked to infertility, sex-specific deficiencies, and several cancers. Recently, HROB has been identified as a critical cofactor of MCM8/9; however, the mechanism underlying activation of MCM8/9 DNA binding and unwinding remain unclear. Here, we present dynamic structures of MCM8/9 with DNA, HROB and ATP analogs using cryo-electron microscopy. DNA binding induces a pronounced rotational rearrangement between the N-terminal DNA binding and C-terminal AAA ATPase domains, reorganizing DNA-binding loops into a staircase configuration that supports DNA engagement. Remarkably, HROB associates with both halves of the heterohexamer and drives a similar rotation prior DNA binding for localizing MCM8/9 to sites of crosslink damage and unwinding, culminating in a unified mechanistic model for MCM8/9 helicase function and its activation by HROB. - Source: PubMed
Publication date: 2026/04/29
Li ChuxuanTo ColinAdeleke Temitope MMcKinzey David RGao YangTrakselis Michael A - MCM8 and MCM9 form a hexameric helicase critical for homologous recombination (HR). While their variants are strongly associated with premature ovarian insufficiency (POI), with many clustering within their AAA+ ATPase domains, the requirement for their helicase activity remains unknown. Here, we show that MCM8-9's helicase activity is essential for ovarian reserve preservation and POI prevention. Using a series of helicase-deficient mouse models, we demonstrate that this activity is dispensable for meiotic recombination but critically required for mitotic HR and primordial germ cell (PGC) development. The two distinct ATPase active sites of MCM8-9 exhibit marked functional asymmetry, a property regulated by residues within their Walker B motifs. Despite this asymmetry, both ATPase active sites are equally essential for MCM8-9's function in HR, PGC development, ovarian reserve preservation, and POI prevention. Our findings establish a direct mechanistic link between compromised MCM8-9 helicase activity and POI pathogenesis through its essential role in PGC development. - Source: PubMed
Publication date: 2026/05/05
Jiao XiaofeiLi ZhifangTang ZhenghuiXu JunLu Lin-YuLiu Yidan - Meiotic DNA double-strand break (DSB) formation and repair by homologous recombination is crucial for ensuring proper chromosome segregation. In mice, the mini-chromosome maintenance family protein, MCM8, has been proposed to function in meiotic recombination and its loss leads to infertility, but the underlying mechanisms are poorly understood. Here we used cytological and genomic assays to infer the role of MCM8 during meiotic recombination in mouse spermatocytes. We show that MCM8-deficient spermatocytes exhibit increased levels of SPO11-dependent DSBs at recombination hotspots during early prophase. DSBs are resected normally and accumulate strand-exchange proteins. However, downstream recombination intermediates are barely detected and recombination intermediate-associated MutSgamma foci do not form efficiently. Consistent with a role in early recombination intermediate processing, MCM8 binds to displacement loop (D-loop) structures . We propose that MCM8 controls meiotic recombination in at least two ways. MCM8 participates in regulating meiotic DSB number. Further, MCM8 plays a role in the formation and/or stability of post-resection recombination intermediates, steps that are critical for DSB repair via recombination and for efficient synapsis of homologous chromosomes during mouse meiosis. - Source: PubMed
Publication date: 2026/03/30
Surarapu Lava KumarTilton KevinStritto Maria Rosaria DelloAcharya AnanyaMenendez Andrea MartonLu MinShaheen NajmaLiang ShunIyer MythriCejka PetrPratto FlorenciaJain Devanshi - Primary liver cancer ranks among the most prevalent and refractory malignant tumors globally. This investigation delves into the role of Epstein-Barr virus nuclear antigen 2-binding protein (EBP2) in hepatocellular carcinoma (HCC). Significantly, EBP2 exhibits marked overexpression in HCC tissues, a finding that correlates with advanced tumor staging and unfavorable prognostic outcomes. In HCC cells, EBP2 silencing led to attenuated proliferation, enhanced apoptosis, and reduced migratory capacity, coupled with reversal of epithelial-mesenchymal transition (EMT). In vivo studies further demonstrated that EBP2 depletion potently suppressed tumor growth in xenograft models. Mechanistically, EBP2 interacts with CENPA to transcriptionally upregulate minichromosome maintenance protein family member 8 (MCM8), thereby stabilizing the MCM8/MCM9 complex and enhancing homologous recombination-mediated DNA repair. Functional rescue experiments revealed that MCM8 overexpression abrogated the suppressive effects of EBP2 knockdown on HCC cell proliferation and migration. In parallel, EBP2 regulates HMGB1 expression through the CENPA/YY1 transcriptional complex, thereby participating in the progression of HCC. Collectively, these findings highlight EBP2 as a crucial regulator of HCC progression via the dual axes-EBP2-CENPA-MCM8 and EBP2-CENPA/YY1-HMGB1, offering a promising therapeutic target for HCC intervention. - Source: PubMed
Publication date: 2026/04/04
Ma EnsiXing HaoSun ChaoZhang QuanbaoShen ConghuanZhan YangyangLi JianhuaLi LiXue HongyuanLi RuidongTeng FeiTao Yifeng - The Homologous Recombination Factor With OB-Fold (HROB) plays a role in homologous recombination and DNA replication, where it enhances the MCM8-MCM9 helicase complex activity. Recent findings link biallelic germline HROB variants to primary gonadal insufficiency (hypergonadotropic hypogonadism), a phenotype also associated with MCM8/MCM9 deficiency. Here, we describe a family where two individuals with biallelic HROB variants presented with hypergonadotropic hypogonadism and colonic polyposis. Exome sequencing identified three unique HROB variants: a likely pathogenic nonsense variant (c.1267C>T [p.(Gln423*)]) in exon four, and two missense variants (c.1363C>G [p.(Leu455Val)] and c.1318A>G [p.(Ser440Gly)]) in exon five. RNA analysis and protein mapping indicate that the nonsense variant is likely pathogenic, whereas the missense variants remain of uncertain significance. Mutational signature analysis of polyposis tissue did not reveal signatures directly linked to HROB deficiency, yet a review of published cases and analyses of cohorts with unexplained polyposis/cancer identified additional individuals with HROB variants exhibiting hypergonadotropic hypogonadism or colonic polyposis. These findings reinforce the association between biallelic germline HROB variants and hypergonadotropic hypogonadism and suggest a potential role in colonic polyposis predisposition. We recommend incorporating HROB into diagnostic gene panels for hypergonadotropic hypogonadism, especially in cases where colonic polyposis is also present. Furthermore, we emphasize the importance of additional studies to comprehensively characterize HROB's phenotypic impact and assess its contribution to disease risk. - Source: PubMed
Publication date: 2026/03/25
Helderman Noah CTops Carli MLegebeke JelmerYang TingGay Marcos DíazTerlouw DianthaLashley Lisa E E L OAretz StefanSommer Anna KTerradas MarionaValle Laurade Voer Richarda MAlexandrov Ludmil BMorreau Hansvan Wezel TomNielsen Maartje