Structural Basis for Error-free Replication of Oxidatively Damaged DNA by Yeast DNA Polymerase η

Timothy D. Silverstein, Rinku Jain, Robert E. Johnson, Louise Prakash, Satya Prakash, Aneel K. Aggarwal

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

7,8-dihydro-8-oxoguanine (8-oxoG) adducts are formed frequently by the attack of oxygen-free radicals on DNA. They are among the most mutagenic lesions in cells because of their dual coding potential, where, in addition to normal base-pairing of 8-oxoG(anti) with dCTP, 8-oxoG in the syn conformation can base pair with dATP, causing G to T transversions. We provide here for the first time a structural basis for the error-free replication of 8-oxoG lesions by yeast DNA polymerase η (Polη). We show that the open active site cleft of Polη can accommodate an 8-oxoG lesion in the anti conformation with only minimal changes to the polymerase and the bound DNA: at both the insertion and post-insertion steps of lesion bypass. Importantly, the active site geometry remains the same as in the undamaged complex and provides a basis for the ability of Polη to prevent the mutagenic replication of 8-oxoG lesions in cells.

Original languageEnglish (US)
Pages (from-to)1463-1470
Number of pages8
JournalStructure
Volume18
Issue number11
DOIs
StatePublished - Nov 10 2010

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DNA-Directed DNA Polymerase
Base Pairing
Catalytic Domain
Yeasts
DNA
Free Radicals
Reactive Oxygen Species
7,8-dihydro-8-oxoguanine
2'-deoxycytidine 5'-triphosphate

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Structural Basis for Error-free Replication of Oxidatively Damaged DNA by Yeast DNA Polymerase η. / Silverstein, Timothy D.; Jain, Rinku; Johnson, Robert E.; Prakash, Louise; Prakash, Satya; Aggarwal, Aneel K.

In: Structure, Vol. 18, No. 11, 10.11.2010, p. 1463-1470.

Research output: Contribution to journalArticle

Silverstein, Timothy D. ; Jain, Rinku ; Johnson, Robert E. ; Prakash, Louise ; Prakash, Satya ; Aggarwal, Aneel K. / Structural Basis for Error-free Replication of Oxidatively Damaged DNA by Yeast DNA Polymerase η. In: Structure. 2010 ; Vol. 18, No. 11. pp. 1463-1470.
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