DNA polymerase ε relies on a unique domain for efficient replisome assembly and strand synthesis Journal Article
| Authors: | Meng, X.; Wei, L.; Devbhandari, S.; Zhang, T.; Xiang, J.; Remus, D.; Zhao, X. |
| Article Title: | DNA polymerase ε relies on a unique domain for efficient replisome assembly and strand synthesis |
| Abstract: | DNA polymerase epsilon (Pol ε) is required for genome duplication and tumor suppression. It supports both replisome assembly and leading strand synthesis; however, the underlying mechanisms remain to be elucidated. Here we report that a conserved domain within the Pol ε catalytic core influences both of these replication steps in budding yeast. Modeling cancer-associated mutations in this domain reveals its unexpected effect on incorporating Pol ε into the four-member pre-loading complex during replisome assembly. In addition, genetic and biochemical data suggest that the examined domain supports Pol ε catalytic activity and symmetric movement of replication forks. Contrary to previously characterized Pol ε cancer variants, the examined mutants cause genome hyper-rearrangement rather than hyper-mutation. Our work thus suggests a role of the Pol ε catalytic core in replisome formation, a reliance of Pol ε strand synthesis on a unique domain, and a potential tumor-suppressive effect of Pol ε in curbing genome re-arrangements. © 2020, The Author(s). |
| Keywords: | controlled study; unclassified drug; gene mutation; mutation; nonhuman; flow cytometry; dna replication; dna synthesis; protein domain; phenotype; cell cycle s phase; protein assembly; genetic variability; dna; gene rearrangement; amino acid sequence; conserved sequence; western blotting; immunoprecipitation; genome; mutation rate; yeast; saccharomycetales; gene dosage; sequence homology; tumor; rna polymerase ii; cell cycle g1 phase; pulsed field gel electrophoresis; budding yeast; southern blotting; dna directed dna polymerase epsilon; replisome; transcription factor rel; peptides and proteins; biochemical composition; g1 phase cell cycle checkpoint; cancer; article; whole genome sequencing; dna replication complex gins protein psf1; dna replication regulator dpb11; dna replication regulator sld2 |
| Journal Title: | Nature Communications |
| Volume: | 11 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2020-01-01 |
| Start Page: | 2437 |
| Language: | English |
| DOI: | 10.1038/s41467-020-16095-x |
| PUBMED: | 32415104 |
| PROVIDER: | scopus |
| PMCID: | PMC7228970 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 June 2020 -- Source: Scopus |
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