ArticleBiochemistry2012
The E288K colon tumor variant of DNA polymerase β is a sequence specific mutator.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 23 citations in OpenAlex.
- Biochemical, structural and mutational landscapes of base excision repair enzymes and cancer: from atomic resolution to tumor signatures.International journal of radiation biology · 2026Review
- The Link Between Human Alkyladenine DNA Glycosylase and Cancer Development.International journal of molecular sciences · 2025Review
- Article
- Melanoma-Derived DNA Polymerase Theta Variants Exhibit Altered DNA Polymerase Activity.Biochemistry · 2024Article
- SNP-Associated Substitutions of Amino Acid Residues in the dNTP Selection Subdomain Decrease Polβ Polymerase Activity.Biomolecules · 2024Article
- Unfilled gaps by polβ lead to aberrant ligation by LIG1 at the downstream steps of base excision repair pathway.Nucleic acids research · 2024Article
- The Role of Natural Polymorphic Variants of DNA Polymerase β in DNA Repair.International journal of molecular sciences · 2022Review
- The base excision repair process: comparison between higher and lower eukaryotes.Cellular and molecular life sciences : CMLS · 2021Review
- NMR and computational methods for molecular resolution of allosteric pathways in enzyme complexes.Biophysical reviews · 2020Review
- Defective Nucleotide Release by DNA Polymerase β Mutator Variant E288K Is the Basis of Its Low Fidelity.Biochemistry · 2017Article
- DNA Polymerase β Cancer-Associated Variant I260M Exhibits Nonspecific Selectivity toward the β-γ Bridging Group of the Incoming dNTP.Biochemistry · 2017Article
- Mechanisms of DNA damage, repair, and mutagenesis.Environmental and molecular mutagenesis · 2017Review
- A Change in the Rate-Determining Step of Polymerization by the K289M DNA Polymerase β Cancer-Associated Variant.Biochemistry · 2017Article
- Base Excision Repair Variants in Cancer.Methods in enzymology · 2017Article
- Base excision repair: a critical player in many games.DNA repair · 2014Review
- Fluorescence resonance energy transfer studies of DNA polymerase β: the critical role of fingers domain movements and a novel non-covalent step during nucleotide selection.The Journal of biological chemistry · 2014Article
- Cellular roles of DNA polymerase beta.The Yale journal of biology and medicine · 2013Review
- Base excision repair.Cold Spring Harbor perspectives in biology · 2013Review
- Catalytic effects of mutations of distant protein residues in human DNA polymerase β: theory and experiment.Biochemistry · 2012Article
- Transcriptional profiling reveals elevated Sox2 in DNA polymerase ß null mouse embryonic fibroblasts.American journal of cancer research · 2012Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
DNA polymerase β (pol β) is the main polymerase involved in base excision repair (BER), which is a pathway responsible for the repair of tens of thousands of DNA lesions per cell per day. Our recent efforts in sequencing colon tumors showed that 40% of the tumors sequenced possessed a variant in the coding region of the POLB gene; one of these variants is E288K. Expression of the E288K variant in cells leads to an increase in the frequency of mutations at AT base pairs. In vitro, the E288K variant is as active as and binds one-base-gapped DNA with the same affinity as wild-type pol β. Single-turnover kinetic data for the E288K variant show that its mutator phenotype is specific for misincorporating opposite template A up to 6-fold more than the wild-type enzyme and that this is due to a decrease in the degree of discrimination in nucleotide binding. Molecular modeling suggests that the substitution of Lys at position 288 causes the polymerase to adopt a more open conformation, which may be disrupting the nucleotide binding pocket. This may explain the reduced degree of discrimination at the level of nucleotide binding. The enhanced mutagenesis of the E288K variant could lead to genomic instability and ultimately a malignant tumor phenotype.
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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.