Knockdown of human MCM10 exhibits delayed and incomplete chromosome replication

Park, Jong Hoon; Bang, Sung Woong; Jeon, Yongho; Kang, Sung-Myung; Hwang, Deog Su

doi:10.1016/j.bbrc.2007.11.003

Cited by 24 publications

(18 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Immunodepletion removed >99% of total Mcm10 from the extract, and no Mcm10 was detectable on chromatin assembled in the depleted extract. Our results are consistent with studies in other metazoan cell types, where knockdown of Mcm10 by RNAi in C. elegans , 57 Drosophila KC cells 11 and Hela cells 30 resulted in no major block to bulk DNA replication. More dramatically, Drosophila Mcm10 mutants were not defective for adult cell proliferation, though they were essential for embryo viability and tissue types, like compound eye, for replication and differentiation 58 …”

Section: Resultssupporting

confidence: 92%

Xenopus Mcm10 is a CDK-substrate required for replication fork stability

et al. 2016

View full text Add to dashboard Cite

During S phase, following activation of the S phase CDKs and the DBF4-dependent kinases (DDK), double hexamers of Mcm2-7 at licensed replication origins are activated to form the core replicative helicase. Mcm10 is one of several proteins that have been implicated from work in yeasts to play a role in forming a mature replisome during the initiation process. Mcm10 has also been proposed to play a role in promoting replisome stability after initiation has taken place. The role of Mcm10 is particularly unclear in metazoans, where conflicting data has been presented. Here, we investigate the role and regulation of Mcm10 in Xenopus egg extracts. We show that Xenopus Mcm10 is recruited to chromatin late in the process of replication initiation and this requires prior action of DDKs and CDKs. We also provide evidence that Mcm10 is a CDK substrate but does not need to be phosphorylated in order to associate with chromatin. We show that in extracts depleted of more than 99% of Mcm10, the bulk of DNA replication still occurs, suggesting that Mcm10 is not required for the process of replication initiation. However, in extracts depleted of Mcm10, the replication fork elongation rate is reduced. Furthermore, the absence of Mcm10 or its phosphorylation by CDK results in instability of replisome proteins on DNA, which is particularly important under conditions of replication stress.

show abstract

Section: Resultssupporting

confidence: 92%

Xenopus Mcm10 is a CDK-substrate required for replication fork stability

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Mcm10, among other replication proteins, was also identified in a second, independent screen for regulators of DSB repair, in which nuclear bodies of the repair protein 53BP1 in U2OS cells were used as a readout for DSBs [55]. These results confirmed preceding studies from two different laboratories, which performed targeted knockdown of Mcm10 in HeLa and U2OS cells to demonstrate that the loss of Mcm10 compromises the ability to complete DNA replication, causes a dramatic increase of DSBs, and triggers checkpoint activation or apoptosis in large parts of the population [31, 56, 57]. Altogether, these data are compatible with the idea that Mcm10 controls multiple processes during DNA replication and actively contributes to the stability of the eukaryotic replication fork.…”

Section: Figuresupporting

confidence: 81%

Enigmatic roles of Mcm10 in DNA replication

Thu

Bielinsky

2013

Trends in Biochemical Sciences

View full text Add to dashboard Cite

Mcm10 is required for DNA replication in all eukaryotes. While 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. Although 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.

show abstract

“…Moreover, genetic studies implicate regulatory interactions between Mcm10 and Mcm2-7 (44,105,194). Even though conditional alleles of MCM10 do not cause a catastrophic loss of fork progression as seen in Cdc45 or GINS mutants, they do cause lethality with associated replication fork defects; forks pause when they reach adjacent unfired origins of replication (177).…”

Section: Possible Role Of Replication Factors During Mcm2-7 Activatiomentioning

confidence: 99%

The Mcm Complex: Unwinding the Mechanism of a Replicative Helicase

Bochman

Schwacha

2009

Microbiol Mol Biol Rev

293

278

View full text Add to dashboard Cite

SUMMARY The Mcm2-7 complex serves as the eukaryotic replicative helicase, the molecular motor that both unwinds duplex DNA and powers fork progression during DNA replication. Consistent with its central role in this process, much prior work has illustrated that Mcm2-7 loading and activation are landmark events in the regulation of DNA replication. Unlike any other hexameric helicase, Mcm2-7 is composed of six unique and essential subunits. Although the unusual oligomeric nature of this complex has long hampered biochemical investigations, recent advances with both the eukaryotic as well as the simpler archaeal Mcm complexes provide mechanistic insight into their function. In contrast to better-studied homohexameric helicases, evidence suggests that the six Mcm2-7 complex ATPase active sites are functionally distinct and are likely specialized to accommodate the regulatory constraints of the eukaryotic process.

show abstract

Knockdown of human MCM10 exhibits delayed and incomplete chromosome replication

Cited by 24 publications

References 23 publications

Xenopus Mcm10 is a CDK-substrate required for replication fork stability

Xenopus Mcm10 is a CDK-substrate required for replication fork stability

Enigmatic roles of Mcm10 in DNA replication

The Mcm Complex: Unwinding the Mechanism of a Replicative Helicase

Contact Info

Product

Resources

About