Human DNA polymerase ι incorporates dCTP opposite template G via a G.C+ hoogsteen base pair

Deepak T. Nair, Robert E. Johnson, Louise Prakash, Satya Prakash, Aneel K. Aggarwal

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Human DNA polymerase ι (hPolι), a member of the Y family of DNA polymerases, differs in remarkable ways from other DNA polymerases, incorporating correct nucleotides opposite template purines with a much higher efficiency and fidelity than opposite template pyrimidines. We present here the crystal structure of hPolι bound to template G and incoming dCTP, which reveals a G.C+ Hoogsteen base pair in a DNA polymerase active site. We show that the hPolι active site has evolved to favor Hoogsteen base pairing, wherein the template sugar is fixed in a cavity that reduces the C1′-C1′ distance across the nascent base pair from ∼10.5 Å in other DNA polymerases to 8.6 Å in hPolι. The rotation of G from anti to syn is then largely in response to this curtailed C1′-C1′ distance. A G.C+ Hoogsteen base pair suggests a specific mechanism for hPolι's ability to bypass N2-adducted guanines that obstruct replication.

Original languageEnglish (US)
Pages (from-to)1569-1577
Number of pages9
JournalStructure
Volume13
Issue number10
DOIs
StatePublished - Oct 2005

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DNA-Directed DNA Polymerase
Base Pairing
Catalytic Domain
Pyrimidines
Purines
Aptitude
2'-deoxycytidine 5'-triphosphate
Guanine
Nucleotides
Efficiency

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

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Human DNA polymerase ι incorporates dCTP opposite template G via a G.C+ hoogsteen base pair. / Nair, Deepak T.; Johnson, Robert E.; Prakash, Louise; Prakash, Satya; Aggarwal, Aneel K.

In: Structure, Vol. 13, No. 10, 10.2005, p. 1569-1577.

Research output: Contribution to journalArticle

Nair, Deepak T. ; Johnson, Robert E. ; Prakash, Louise ; Prakash, Satya ; Aggarwal, Aneel K. / Human DNA polymerase ι incorporates dCTP opposite template G via a G.C+ hoogsteen base pair. In: Structure. 2005 ; Vol. 13, No. 10. pp. 1569-1577.
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