Yeast DNA polymerase η makes functional contacts with the DNA minor groove only at the incoming nucleoside triphosphate

M. Todd Washington, William T. Wolfle, Thomas E. Spratt, Louise Prakash, Satya Prakash

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

DNA polymerase η (Polη) functions in the proficient bypass of a variety of DNA lesions. Relative to the replicative polymerases, Polη 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 Polη also makes such functionally important contacts with the DNA minor groove, here we examine the effects on Polη-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 Polη makes only a single functional contact with the DNA minor groove at the position of the incoming nucleotide; in this regard, Polη differs from high-fidelity DNA polymerases that are unable to replicate through DNA lesions. These results help explain the proficient ability of Polη for bypassing distorting DNA lesions.

Original languageEnglish (US)
Pages (from-to)5113-5118
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number9
DOIs
StatePublished - Apr 29 2003

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DNA-Directed DNA Polymerase
Nucleosides
Yeasts
DNA
Nucleotides
triphosphoric acid
Guanine
Hydrogen
X-Rays

ASJC Scopus subject areas

  • Genetics
  • General

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Yeast DNA polymerase η makes functional contacts with the DNA minor groove only at the incoming nucleoside triphosphate. / Washington, M. Todd; Wolfle, William T.; Spratt, Thomas E.; Prakash, Louise; Prakash, Satya.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 9, 29.04.2003, p. 5113-5118.

Research output: Contribution to journalArticle

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abstract = "DNA polymerase η (Polη) functions in the proficient bypass of a variety of DNA lesions. Relative to the replicative polymerases, Polη 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 Polη also makes such functionally important contacts with the DNA minor groove, here we examine the effects on Polη-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 Polη makes only a single functional contact with the DNA minor groove at the position of the incoming nucleotide; in this regard, Polη differs from high-fidelity DNA polymerases that are unable to replicate through DNA lesions. These results help explain the proficient ability of Polη for bypassing distorting DNA lesions.",
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