ArticleBiochemistry2008
The Asp285 variant of DNA polymerase beta extends mispaired primer termini via increased nucleotide binding.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 26 citations in OpenAlex.
- Zebrafish Polymerase Theta and human Polymerase Theta: Orthologues with homologous function.PloS one · 2025Article
- Article
- The Impact of SNP-Induced Amino Acid Substitutions L19P and G66R in the dRP-Lyase Domain of Human DNA Polymerase β on Enzyme Activities.International journal of molecular sciences · 2024Article
- Human Polβ Natural Polymorphic Variants G118V and R149I Affects Substate Binding and Catalysis.International journal of molecular sciences · 2023Article
- The Role of Natural Polymorphic Variants of DNA Polymerase β in DNA Repair.International journal of molecular sciences · 2022Review
- A pre-catalytic non-covalent step governs DNA polymerase β fidelity.Nucleic acids research · 2019Article
- I260Q DNA polymerase β highlights precatalytic conformational rearrangements critical for fidelity.Nucleic acids research · 2018Article
- Defective Nucleotide Release by DNA Polymerase β Mutator Variant E288K Is the Basis of Its Low Fidelity.Biochemistry · 2017Article
- A Change in the Rate-Determining Step of Polymerization by the K289M DNA Polymerase β Cancer-Associated Variant.Biochemistry · 2017Article
- DNA Polymerase Beta Germline Variant Confers Cellular Response to Cisplatin Therapy.Molecular cancer research : MCR · 2017Article
- 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
- The S229L colon tumor-associated variant of DNA polymerase β induces cellular transformation as a result of decreased polymerization efficiency.The Journal of biological chemistry · 2014Article
- The steric gate of DNA polymerase ι regulates ribonucleotide incorporation and deoxyribonucleotide fidelity.The Journal of biological chemistry · 2014Article
- A remote palm domain residue of RB69 DNA polymerase is critical for enzyme activity and influences the conformation of the active site.PloS one · 2013Article
- Catalytic effects of mutations of distant protein residues in human DNA polymerase β: theory and experiment.Biochemistry · 2012Article
- Human POLB gene is mutated in high percentage of colorectal tumors.The Journal of biological chemistry · 2012Article
- Colon cancer-associated DNA polymerase β variant induces genomic instability and cellular transformation.The Journal of biological chemistry · 2012Article
- The E288K colon tumor variant of DNA polymerase β is a sequence specific mutator.Biochemistry · 2012Article
- Unfavorable electrostatic and steric interactions in DNA polymerase β E295K mutant interfere with the enzyme's pathway.Journal of the American Chemical Society · 2012Article
- The human gastric cancer-associated DNA polymerase β variant D160N is a mutator that induces cellular transformation.DNA repair · 2012Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Endogenous DNA damage occurs at a rate of at least 20,000 lesions per cell per day. Base excision repair (BER) is a key pathway for maintaining genome stability. Several pol beta variants were identified as conferring resistance to 3'-azido-3'-deoxythymidine (AZT) in Escherichia coli (Kosa et al. (1999) J. Biol. Chem. 274, 3851-3858). Detailed biochemical studies on one of these AZT-resistant variants, His285 to Asp, have shown that the H285D variant of pol beta possesses pre-steady-state kinetics that are similar to the wild-type polymerase. In gap filling assays with 5-bp gapped DNA, H285D showed a slight mutator phenotype. In depth single turnover kinetic analysis revealed that H285D is much more efficient than wild-type pol beta at extending mispaired primer termini. This mispair extension property of H285D is attributed to a greatly increased binding to the next correct nucleotide in the presence of a mispair. This change in K d(dNTP),app is not accompanied by a change in k pol; values for k pol are the same for both H285D and wild-type. Close examination of available structural data, as well as molecular modeling, has shown that residue 285 is able to make several stabilizing contacts in the fingers domain of the polymerase, and the introduction of a negatively charged side chain could have important effects on the enzyme. It is postulated that the loss of the contact between His285, Lys289, and Ile323 is responsible for the ability of H285D to extend mispairs through disruption of contacts near the C-terminal end of pol beta and propagation into the nucleotide binding pocket.
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