title: Yeast DNA polymerase eta utilizes an induced-fit mechanism of nucleotide incorporation.
abstract: DNA polymerase eta (Poleta) is unique among eukaryotic DNA polymerases in its proficient ability to replicate through distorting DNA lesions, and Poleta synthesizes DNA with a low fidelity. Here, we use pre-steady-state kinetics to investigate the mechanism of nucleotide incorporation by Poleta and show that it utilizes an induced-fit mechanism to selectively incorporate the correct nucleotide. Poleta discriminates poorly between the correct and incorrect nucleotide at both the initial nucleotide binding step and at the subsequent induced-fit conformational change step, which precedes the chemical step of phosphodiester bond formation. This property enables Poleta to bypass lesions with distorted DNA geometries, and it bestows upon the enzyme a low fidelity.
authors.affiliation: Sealy Center for Molecular Science, University of Texas Medical Branch at Galveston, 6.104 Blocker Medical Research Building, 11th and Mechanic Streets, Galveston, TX 77555, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Washington
authors.forename: L
authors.initials: L
authors.lastname: Prakash
authors.forename: S
authors.initials: S
authors.lastname: Prakash
mesh_terms: D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D009711:Nucleotides / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics*; D013379:Substrate Specificity; D000099270:Y-Family DNA Polymerases
chemical_list: D004247:DNA; D004259:DNA-Directed DNA Polymerase; D009711:Nucleotides; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases