Yeast DNA polymerase eta makes functional contacts with the DNA minor groove only at the incoming nucleoside triphosphate.
Journal
  Proceedings of the National Academy of Sciences of the United States of America.
Citation
  Proc Natl Acad Sci U S A. 100(9):5113-8
Publication date
  2003 Apr 29
Authors
  Washington MT
Wolfle WT
Spratt TE
Prakash L
Prakash S
Investigators
  Thomas Spratt
Grant agencies
  National Cancer Institute
National Institute of General Medical Sciences
Grants
  NCI CA75074
NIGMS GM19261
MeSH headings
  DNA, Fungal
DNA-Directed DNA Polymerase
Nucleosides
Saccharomyces cerevisiae
MeSH qualifiers
  metabolism
enzymology
Abstract
  DNA polymerase eta (Pol eta) functions in the proficient bypass of a variety of DNA lesions. Relative to the replicative polymerases, Pol eta has a greater tolerance for distorted DNA geometries and possesses a low fidelity. X-ray crystal structures and studies with nucleotide analogs have implicated interactions with the DNA minor groove as being crucial for the high fidelity of replicative DNA polymerases. To determine whether Pol eta also makes such functionally important contacts with the DNA minor groove, here we examine the effects on Pol eta-catalyzed nucleotide incorporation when 3-deazaguanine, a base analog that lacks the ability to form minor-groove hydrogen bonds with the protein, is substituted for guanine at various positions in the DNA. From these studies, we conclude that Pol eta makes only a single functional contact with the DNA minor groove at the position of the incoming nucleotide; in this regard, Pol eta differs from high-fidelity DNA polymerases that are unable to replicate through DNA lesions. These results help explain the proficient ability of Pol eta for bypassing distorting DNA lesions.
Medline ID
  22608587