ArticleDNA repair2013
Human Pol ε-dependent replication errors and the influence of mismatch repair on their correction.
Article in DNA repair, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 21 citations in OpenAlex.
- A phase II clinical trial of toripalimab in advanced solid tumors with polymerase epsilon/polymerase delta (POLE/POLD1) mutation.Signal transduction and targeted therapy · 2024Trial
- Comprehensive analysis of POLE and POLD1 Gene Variations identifies cancer patients potentially benefit from immunotherapy in Chinese population.Scientific reports · 2019Trial
- Functional Characterization ofDiseases (Basel, Switzerland) · 2026Article
- Neoadjuvant chemoradiotherapy combined with immunotherapy: a promising strategy for MSS/pMMR locally advanced rectal cancer.Medical oncology (Northwood, London, England) · 2025Review
- Pembrolizumab and Trastuzumab in High Tumor Mutational Burden and POLE-Mutated HER2-Positive Refractory Breast Cancer.The oncologist · 2022Article
- Biomarkers for predicting the efficacy of immune checkpoint inhibitors.Journal of Cancer · 2022Review
- Maternal Low-Protein Diet Deregulates DNA Repair and DNA Replication Pathways in Female Offspring Mammary Gland Leading to Increased Chemically Induced Rat Carcinogenesis in Adulthood.Frontiers in cell and developmental biology · 2021Article
- FDA-Approved and Emerging Next Generation Predictive Biomarkers for Immune Checkpoint Inhibitors in Cancer Patients.Frontiers in oncology · 2021Review
- Review
- Article
- Human DNA polymerase delta double-mutant D316A;E318A interferes with DNA mismatch repair in vitro.Nucleic acids research · 2017Article
- Replicative DNA polymerase defects in human cancers: Consequences, mechanisms, and implications for therapy.DNA repair · 2017Review
- Nucleotide selectivity defect and mutator phenotype conferred by a colon cancer-associated DNA polymerase δ mutation in human cells.Oncogene · 2017Article
- Heterozygous colon cancer-associated mutations of SAMHD1 have functional significance.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- A novel mutation in the POLE2 gene causing combined immunodeficiency.The Journal of allergy and clinical immunology · 2016Article
- Eukaryotic genome instability in light of asymmetric DNA replication.Critical reviews in biochemistry and molecular biology · 2016Review
- Colon cancer-associated mutator DNA polymerase δ variant causes expansion of dNTP pools increasing its own infidelity.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Article
- Replicative DNA polymerase mutations in cancer.Current opinion in genetics & development · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in human DNA polymerase (Pol) ε, one of three eukaryotic Pols required for DNA replication, have recently been found associated with an ultramutator phenotype in tumors from somatic colorectal and endometrial cancers and in a familial colorectal cancer. Possibly, Pol ε mutations reduce the accuracy of DNA synthesis, thereby increasing the mutational burden and contributing to tumor development. To test this possibility in vivo, we characterized an active site mutant allele of human Pol ε that exhibits a strong mutator phenotype in vitro when the proofreading exonuclease activity of the enzyme is inactive. This mutant has a strong bias toward mispairs opposite template pyrimidine bases, particularly T • dTTP mispairs. Expression of mutant Pol ε in human cells lacking functional mismatch repair caused an increase in mutation rate primarily due to T • dTTP mispairs. Functional mismatch repair eliminated the increased mutagenesis. The results indicate that the mutant Pol ε causes replication errors in vivo, and is at least partially dominant over the endogenous, wild type Pol ε. Since tumors from familial and somatic colorectal patients arise with Pol ε mutations in a single allele, are microsatellite stable and have a large increase in base pair substitutions, our data are consistent with a Pol ε mutation requiring additional factors to promote tumor development.
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Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.