The N-terminus of Mcm10 is important for interaction with the 9-1-1 clamp and in resistance to DNA damage

Robert C. Alver, Tianji Zhang, Ajeetha Josephrajan, Brandy L. Fultz, Chance J. Hendrix, Sapna Das-Bradoo, Anja Katrin Bielinsky

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20 Scopus citations


Accurate replication of the genome requires the evolutionarily conserved minichromosome maintenance protein, Mcm10. Although the details of the precise role of Mcm10 in DNA replication are still debated, it interacts with the Mcm2-7 core helicase, the lagging strand polymerase, DNA polymerase-α and the replication clamp, proliferating cell nuclear antigen. Loss of these interactions caused by the depletion of Mcm10 leads to chromosome breakage and cell cycle checkpoint activation. However, whether Mcm10 has an active role in DNA damage prevention is unknown. Here, we present data that establish a novel role of the N-terminus of Mcm10 in resisting DNA damage. We show that Mcm10 interacts with the Mec3 subunit of the 9-1-1 clamp in response to replication stress evoked by UV irradiation or nucleotide shortage. We map the interaction domain with Mec3 within the N-terminal region of Mcm10 and demonstrate that its truncation causes UV light sensitivity. This sensitivity is not further enhanced by a deletion of MEC3, arguing that MCM10 and MEC3 operate in the same pathway. Since Rad53 phosphorylation in response to UV light appears to be normal in N-terminally truncated mcm10 mutants, we propose that Mcm10 may have a role in replication fork restart or DNA repair.

Original languageEnglish (US)
Pages (from-to)8389-8404
Number of pages16
JournalNucleic acids research
Issue number13
StatePublished - Jul 29 2014

Bibliographical note

Funding Information:
National Institutes of Health [R01GM074917 to AK.B.] and [8P20GM103447 to S.D-B.]; Scholarship of the Leukemia and Lymphoma Society [1023-09 to AK.B.]. Funding for openaccess charge: National Institutes of Health grant [R01GM074917]. Conflict of interest statement. None declared.


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