5j2k Citations

Structures of DNA Polymerase Mispaired DNA Termini Transitioning to Pre-catalytic Complexes Support an Induced-Fit Fidelity Mechanism.

Structure 24 1863-1875 (2016)
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Cited: 19 times
EuropePMC logo PMID: 27642161

Abstract

High-fidelity DNA synthesis requires that polymerases display a strong preference for right nucleotide insertion. When the wrong nucleotide is inserted, the polymerase deters extension from the mismatched DNA terminus. Twenty-three crystallographic structures of DNA polymerase β with terminal template-primer mismatches were determined as binary DNA and ternary pre-catalytic substrate complexes. These structures indicate that the mismatched termini adopt various distorted conformations that attempt to satisfy stacking and hydrogen-bonding interactions. The binary complex structures indicate an induced strain in the mismatched template nucleotide. Addition of a non-hydrolyzable incoming nucleotide stabilizes the templating nucleotide with concomitant strain in the primer terminus. Several dead-end ternary complex structures suggest that DNA synthesis might occur as the enzyme transitions from an open to a closed complex. The structures are consistent with an induced-fit mechanism where a mismatched terminus is misaligned relative to the correct incoming nucleotide to deter or delay further DNA synthesis.

Articles - 5j2k mentioned but not cited (1)



Reviews citing this publication (2)

  1. Evolutionary dynamics and significance of multiple subclonal mutations in cancer. Beckman RA, Loeb LA. DNA Repair (Amst) 56 7-15 (2017)
  2. History of DNA polymerase β X-ray crystallography. Whitaker AM, Freudenthal BD. DNA Repair (Amst) 93 102928 (2020)

Articles citing this publication (16)

  1. Activation of the mismatch-specific endonuclease EndoMS/NucS by the replication clamp is required for high fidelity DNA replication. Ishino S, Skouloubris S, Kudo H, l'Hermitte-Stead C, Es-Sadik A, Lambry JC, Ishino Y, Myllykallio H. Nucleic Acids Res 46 6206-6217 (2018)
  2. Modulating the DNA polymerase β reaction equilibrium to dissect the reverse reaction. Shock DD, Freudenthal BD, Beard WA, Wilson SH. Nat Chem Biol 13 1074-1080 (2017)
  3. Capturing a mammalian DNA polymerase extending from an oxidized nucleotide. Whitaker AM, Smith MR, Schaich MA, Freudenthal BD. Nucleic Acids Res 45 6934-6944 (2017)
  4. Promutagenicity of 8-Chloroguanine, A Major Inflammation-Induced Halogenated DNA Lesion. Kou Y, Koag MC, Lee S. Molecules 24 E3507 (2019)
  5. The ligation of pol β mismatch insertion products governs the formation of promutagenic base excision DNA repair intermediates. Çağlayan M. Nucleic Acids Res 48 3708-3721 (2020)
  6. Polymorphic G:G mismatches act as hotspots for inducing right-handed Z DNA by DNA intercalation. Satange R, Chuang CY, Neidle S, Hou MH. Nucleic Acids Res 47 8899-8912 (2019)
  7. Uniform Free-Energy Profiles of the P-O Bond Formation and Cleavage Reactions Catalyzed by DNA Polymerases β and λ. Klvaňa M, Bren U, Florián J. J Phys Chem B 120 13017-13030 (2016)
  8. Structural and functional insight into mismatch extension by human DNA polymerase α. Baranovskiy AG, Babayeva ND, Lisova AE, Morstadt LM, Tahirov TH. Proc Natl Acad Sci U S A 119 e2111744119 (2022)
  9. Structures of a DNA Polymerase Inserting Therapeutic Nucleotide Analogues. Schaich MA, Smith MR, Cloud AS, Holloran SM, Freudenthal BD. Chem Res Toxicol 30 1993-2001 (2017)
  10. A pre-catalytic non-covalent step governs DNA polymerase β fidelity. Alnajjar KS, Krylov IS, Negahbani A, Haratipour P, Kashemirov BA, Huang J, Mahmoud M, McKenna CE, Goodman MF, Sweasy JB. Nucleic Acids Res 47 11839-11849 (2019)
  11. DNA polymerase β nucleotide-stabilized template misalignment fidelity depends on local sequence context. Howard MJ, Cavanaugh NA, Batra VK, Shock DD, Beard WA, Wilson SH. J Biol Chem 295 529-538 (2020)
  12. AUF1 Recognizes 8-Oxo-Guanosine Embedded in DNA and Stimulates APE1 Endoribonuclease Activity. Malfatti MC, Codrich M, Dalla E, D'Ambrosio C, Storici F, Scaloni A, Tell G. Antioxid Redox Signal 39 411-431 (2023)
  13. Molecular and structural characterization of oxidized ribonucleotide insertion into DNA by human DNA polymerase β. Smith MR, Alnajjar KS, Hoitsma NM, Sweasy JB, Freudenthal BD. J Biol Chem 295 1613-1622 (2020)
  14. Structure of a DNA polymerase abortive complex with the 8OG:dA base pair at the primer terminus. Batra VK, Wilson SH. Commun Biol 3 348 (2020)
  15. Structures of LIG1 that engage with mutagenic mismatches inserted by polβ in base excision repair. Tang Q, Gulkis M, McKenna R, Çağlayan M. Nat Commun 13 3860 (2022)
  16. Polβ/XRCC1 heterodimerization dictates DNA damage recognition and basal Polβ protein levels without interfering with mouse viability or fertility. Koczor CA, Thompson MK, Sharma N, Prakash A, Sobol RW. DNA Repair (Amst) 123 103452 (2023)