Abstract
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.
Highlights
Genome maintenance is one of the highest priorities for all eukaryotic organisms, a task confounded by the constant assault of intrinsic and environmental factors that damage an organism’s DNA
The L242Y mutant displayed a slightly stronger residual interaction than the other two mutants (Figure 1C), similar to Mcm10 PIP box mutants and proliferating cell nuclear antigen (PCNA) [15]. These results argue that the interaction between Mcm10 and Mec3 is partially mediated through Mcm10’s PIP box
We present data that describe a novel interaction between the replication factor Mcm10 and the 91-1 clamp
Summary
Genome maintenance is one of the highest priorities for all eukaryotic organisms, a task confounded by the constant assault of intrinsic and environmental factors that damage an organism’s DNA. To counteract these factors, cells employ a DNA damage response (DDR), a complex network of signaling proteins that can sense compromised DNA and activate appropriate cellular processes depending on the type and amount of the damage [1]. Mcm is an essential, conserved replication factor [9,10] important in both the initiation and elongation steps of DNA replication. Loss of Mcm protein expression results in induction of DNA breaks as well as checkpoint activation [3,16]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
