Minichromsome maintenance protein 10 (Mcm10) is an essential replication factor that is required for the activation of the Cdc45:Mcm2-7:GINS helicase. Mcm10's ability to bind both ds and ssDNA appears vital for this function. In addition, Mcm10 interacts with multiple players at the replication fork, including DNA polymerase-α and proliferating cell nuclear antigen with which it cooperates during DNA elongation. Mcm10 lacks enzymatic function, but instead provides the replication apparatus with an oligomeric scaffold that likely acts in the coordination of DNA unwinding and DNA synthesis. Not surprisingly, loss of Mcm10 engages checkpoint, DNA repair and SUMO-dependent rescue pathways that collectively counteract replication stress and chromosome breakage. Here, we review Mcm10's structure and function and explain how it contributes to the maintenance of genome integrity.
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http://dx.doi.org/10.1016/j.semcdb.2014.03.017 | DOI Listing |
Nat Commun
December 2024
Department of Biology, Tufts University, Medford, MA, 02155, USA.
Trinucleotide repeats, including Friedreich's ataxia (GAA) repeats, become pathogenic upon expansions during DNA replication and repair. Here, we show that deficiency of the essential replisome component Mcm10 dramatically elevates (GAA) repeat instability in a budding yeast model by loss of proper CMG helicase interaction. Supporting this conclusion, live-cell microscopy experiments reveal increased replication fork stalling at the repeat in mcm10-1 cells.
View Article and Find Full Text PDFGene
February 2025
Cell Biology and Molecular Genetics, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore 575018, India. Electronic address:
Cervical cancer remains a significant health burden worldwide, emphasizing the need for early detection and intervention. DNA replication is perturbed in cancer cells, and the minichromosome maintenance protein 10 plays an important role in origin firing. By analyzing the MCM10 mRNA expression in healthy controls, precancerous lesions, and cervical cancer using qRT-PCR, we can infer if it can be considered a biomarker.
View Article and Find Full Text PDFSci Rep
November 2024
Bioinformatics Lab (Dry), Department of Statistics, University of Rajshahi, Rajshahi, 6205, Bangladesh.
Glioblastoma (GBM) is the most malignant brain cancer and one of the leading causes of cancer-related death globally. So, identifying potential molecular signatures and associated drug molecules are crucial for diagnosis and therapies of GBM. This study suggested GBM-causing ten key genes (ASPM, CCNB2, CDK1, AURKA, TOP2A, CHEK1, CDCA8, SMC4, MCM10, and RAD51AP1) from nine transcriptomics datasets by combining supervised and unsupervised learning results.
View Article and Find Full Text PDFFront Cell Dev Biol
September 2024
Guangdong Key Laboratory for Genome Stability and Disease Prevention, Shenzhen University General Hospital and Medical School, Shenzhen, China.
Mcm10 plays an essential role in the activation of replicative helicase CMG through the cell cycle-regulated interaction with the prototype MCM double hexamer in . In this study, we reported that Mcm10 is phosphorylated by S-phase cyclin-dependent kinases (S-CDKs) at S66, which enhances Mcm10--MCM association during the S phase. S66A single mutation or even deletion of whole N-terminus (a.
View Article and Find Full Text PDFCancer Metastasis Rev
December 2024
Cell Biology and Molecular Genetics (CBMG), Yenepoya Research Centre (YRC), Yenepoya (Deemed to be University), Mangalore, 575018, India.
MCM10 plays a vital role in genome duplication and is crucial for DNA replication initiation, elongation, and termination. It coordinates several proteins to assemble at the fork, form a functional replisome, trigger origin unwinding, and stabilize the replication bubble. MCM10 overexpression is associated with increased aggressiveness in breast, cervical, and several other cancers.
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