Enigmatic Roles of Mcm10 in DNA Replication

Overview

Journal Trends Biochem Sci

Specialty Biochemistry

Date 2013 Jan 22

PMID 23332289

Citations 51

Authors

Yee Mon Thu

Anja-Katrin Bielinsky

Affiliations

Soon will be listed here.

Abstract

Minichromosome maintenance protein 10 (Mcm10) is required for DNA replication in all eukaryotes. Although the exact contribution of Mcm10 to genome replication remains heavily debated, early reports suggested that it promotes DNA unwinding and origin firing. These ideas have been solidified by recent studies that propose a role for Mcm10 in helicase activation. Whereas the molecular underpinnings of this activation step have yet to be revealed, structural data on Mcm10 provide further insight into a possible mechanism of action. The essential role in DNA replication initiation is not mutually exclusive with additional functions that Mcm10 may have as part of the elongation machinery. Here, we review the recent findings regarding the role of Mcm10 in DNA replication and discuss existing controversies.

Citing Articles

Stabilization of expandable DNA repeats by the replication factor Mcm10 promotes cell viability.

Masnovo C, Paleiov Z, Dovrat D, Baxter L, Movafaghi S, Aharoni A Nat Commun. 2024; 15(1):10532.

PMID: 39627228 PMC: 11615337. DOI: 10.1038/s41467-024-54977-6.

Multifaceted role of the DNA replication protein MCM10 in maintaining genome stability and its implication in human diseases.

Ahmed S, Sasikumar J, Laha S, Das S Cancer Metastasis Rev. 2024; 43(4):1353-1371.

PMID: 39240414 DOI: 10.1007/s10555-024-10209-3.

Investigation into in silico and in vitro approaches for inhibitors targeting MCM10 in Leishmania donovani: a comprehensive study.

Saha S, Sharma A, Bhowmik D, Kumar D Mol Divers. 2024; 29(1):575-590.

PMID: 38722455 DOI: 10.1007/s11030-024-10876-y.

RNF4 prevents genomic instability caused by chronic DNA under-replication.

Oram M, Baxley R, Simon E, Lin K, Chang Y, Wang L DNA Repair (Amst). 2024; 135:103646.

PMID: 38340377 PMC: 10948022. DOI: 10.1016/j.dnarep.2024.103646.

A critical threshold of MCM10 is required to maintain genome stability during differentiation of induced pluripotent stem cells into natural killer cells.

Schmit M, Baxley R, Wang L, Hinderlie P, Kaufman M, Simon E Open Biol. 2024; 14(1):230407.

PMID: 38262603 PMC: 10805602. DOI: 10.1098/rsob.230407.

References

Haworth J, Alver R, Anderson M, Bielinsky A . Ubc4 and Not4 regulate steady-state levels of DNA polymerase-α to promote efficient and accurate DNA replication. Mol Biol Cell. 2010; 21(18):3205-19. PMC: 2938386. DOI: 10.1091/mbc.E09-06-0452. View

Matsuoka S, Ballif B, Smogorzewska A, McDonald 3rd E, Hurov K, Luo J . ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007; 316(5828):1160-6. DOI: 10.1126/science.1140321. View

Hart E, Bryant J, Moore K, Aves S . Fission yeast Cdc23 interactions with DNA replication initiation proteins. Curr Genet. 2002; 41(5):342-8. DOI: 10.1007/s00294-002-0316-9. View

Ricke R, Bielinsky A . Mcm10 regulates the stability and chromatin association of DNA polymerase-alpha. Mol Cell. 2004; 16(2):173-85. DOI: 10.1016/j.molcel.2004.09.017. View

Izumi M, Yanagi K, Mizuno T, Yokoi M, Kawasaki Y, Moon K . The human homolog of Saccharomyces cerevisiae Mcm10 interacts with replication factors and dissociates from nuclease-resistant nuclear structures in G(2) phase. Nucleic Acids Res. 2000; 28(23):4769-77. PMC: 115166. DOI: 10.1093/nar/28.23.4769. View

Cobb J, Schleker T, Rojas V, Bjergbaek L, Tercero J, Gasser S . Replisome instability, fork collapse, and gross chromosomal rearrangements arise synergistically from Mec1 kinase and RecQ helicase mutations. Genes Dev. 2005; 19(24):3055-69. PMC: 1315408. DOI: 10.1101/gad.361805. View

Okorokov A, Waugh A, Hodgkinson J, Murthy A, Hong H, Leo E . Hexameric ring structure of human MCM10 DNA replication factor. EMBO Rep. 2007; 8(10):925-30. PMC: 2002553. DOI: 10.1038/sj.embor.7401064. View

Warren E, Huang H, Fanning E, Chazin W, Eichman B . Physical interactions between Mcm10, DNA, and DNA polymerase alpha. J Biol Chem. 2009; 284(36):24662-72. PMC: 2782055. DOI: 10.1074/jbc.M109.020438. View

Xu X, Rochette P, Feyissa E, Su T, Liu Y . MCM10 mediates RECQ4 association with MCM2-7 helicase complex during DNA replication. EMBO J. 2009; 28(19):3005-14. PMC: 2760112. DOI: 10.1038/emboj.2009.235. View

10.

Kawasaki Y, Hiraga S, Sugino A . Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in Saccharomyces cerevisiae. Genes Cells. 2001; 5(12):975-89. DOI: 10.1046/j.1365-2443.2000.00387.x. View

11.

Mayer M, Gygi S, Aebersold R, Hieter P . Identification of RFC(Ctf18p, Ctf8p, Dcc1p): an alternative RFC complex required for sister chromatid cohesion in S. cerevisiae. Mol Cell. 2001; 7(5):959-70. DOI: 10.1016/s1097-2765(01)00254-4. View

12.

Lee C, Liachko I, Bouten R, Kelman Z, Tye B . Alternative mechanisms for coordinating polymerase alpha and MCM helicase. Mol Cell Biol. 2009; 30(2):423-35. PMC: 2798462. DOI: 10.1128/MCB.01240-09. View

13.

Liachko I, Tye B . Mcm10 is required for the maintenance of transcriptional silencing in Saccharomyces cerevisiae. Genetics. 2005; 171(2):503-15. PMC: 1456767. DOI: 10.1534/genetics.105.042333. View

14.

Liang D, Forsburg S . Characterization of Schizosaccharomyces pombe mcm7(+) and cdc23(+) (MCM10) and interactions with replication checkpoints. Genetics. 2001; 159(2):471-86. PMC: 1461838. DOI: 10.1093/genetics/159.2.471. View

15.

van Deursen F, Sengupta S, Piccoli G, Sanchez-Diaz A, Labib K . Mcm10 associates with the loaded DNA helicase at replication origins and defines a novel step in its activation. EMBO J. 2012; 31(9):2195-206. PMC: 3343467. DOI: 10.1038/emboj.2012.69. View

16.

Eisenberg S, Korza G, Carson J, Liachko I, Tye B . Novel DNA binding properties of the Mcm10 protein from Saccharomyces cerevisiae. J Biol Chem. 2009; 284(37):25412-20. PMC: 2757242. DOI: 10.1074/jbc.M109.033175. View

17.

Kaur M, Khan M, Kar A, Sharma A, Saxena S . CRL4-DDB1-VPRBP ubiquitin ligase mediates the stress triggered proteolysis of Mcm10. Nucleic Acids Res. 2012; 40(15):7332-46. PMC: 3424545. DOI: 10.1093/nar/gks366. View

18.

Liachko I, Tye B . Mcm10 mediates the interaction between DNA replication and silencing machineries. Genetics. 2008; 181(2):379-91. PMC: 2644934. DOI: 10.1534/genetics.108.099101. View

19.

Zhu W, Ukomadu C, Jha S, Senga T, Dhar S, Wohlschlegel J . Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication. Genes Dev. 2007; 21(18):2288-99. PMC: 1973143. DOI: 10.1101/gad.1585607. View

20.

Apger J, Reubens M, Henderson L, Gouge C, Ilic N, Zhou H . Multiple functions for Drosophila Mcm10 suggested through analysis of two Mcm10 mutant alleles. Genetics. 2010; 185(4):1151-65. PMC: 2927746. DOI: 10.1534/genetics.110.117234. View