title: Fidelity mechanisms of DNA polymerase beta.
abstract: DNA polymerase 3 (Pol beta) is one of the best characterized eukaryotic DNA polymerases. Pol beta is a member of the X family of DNA polymerases. The Pol beta protein has two catalytic activities: DNA polymerase activity and dRP lyase activity. Pol beta has no known proofreading activity, so its accuracy in vitro results exclusively from the nucleotide selectivity of this enzyme. Presteady-state kinetic analysis has shown that Pol beta functions in nucleotide selectivity predominantly during phosphodiester bond formation, although this enzyme also possesses some ability to discriminate the correct from the incorrect deoxynucleoside triphosphate (dNTP) substrate during ground state binding. Recent results strongly suggest that Pol beta does not employ an induced fit mechanism of nucleotide discrimination. The fidelity of Pol beta appears to be determined through steric exclusion against the incorrect substrate and by the precise positioning of the catalytic residues, DNA, and substrate within the active site of the enzyme. Imprecise positioning of active site residues or DNA can result in the incorporation of the incorrect substrate into DNA. Amino acid residues both distant and near to the active site of Pol beta influence its geometry, suggesting that the movements and positioning of subdomains of Pol beta have a significant impact upon its fidelity.
authors.affiliation: Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Joann B
authors.initials: JB
authors.lastname: Sweasy
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D019951:DNA Polymerase beta / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013912:Threonine / Q000737:chemistry; D013997:Time Factors
chemical_list: D013912:Threonine; D001120:Arginine; D019951:DNA Polymerase beta