title: The N-terminus of Mcm10 is important for interaction with the 9-1-1 clamp and in resistance to DNA damage.
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.
authors: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Robert C
authors: RC
authors: Alver
authors: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Tianji
authors: T
authors: Zhang
authors: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Ajeetha
authors: A
authors: Josephrajan
authors: Department of Natural Sciences, Northeastern State University, 3100 East New Orleans Street, Broken Arrow, OK 74012, USA.
authors: Brandy L
authors: BL
authors: Fultz
authors: Department of Natural Sciences, Northeastern State University, 3100 East New Orleans Street, Broken Arrow, OK 74012, USA.
authors: Chance J
authors: CJ
authors: Hendrix
authors: Department of Natural Sciences, Northeastern State University, 3100 East New Orleans Street, Broken Arrow, OK 74012, USA.
authors: Sapna
authors: S
authors: Das-Bradoo
authors: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA bieli003@umn.edu.
authors: Anja-Katrin
authors: AK
authors: Bielinsky
mesh_terms: D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism; D064110:Minichromosome Maintenance Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021122:Protein Subunits / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C440013:Ddc1 protein, S cerevisiae; C076365:MCM10 protein, S cerevisiae; C099938:MEC3 protein, S cerevisiae; D009687:Nuclear Proteins; D021122:Protein Subunits; C501395:RAD17 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D064110:Minichromosome Maintenance Proteins