DNA Synthesis across an Abasic Lesion by Human DNA Polymerase ι

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

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Abasic sites are among the most abundant DNA lesions formed in human cells, and they present a strong block to replication. DNA polymerase ι (Polι) is one of the few DNA Pols that does not follow the A-rule opposite an abasic site. We present here three structures of human Polι in complex with DNAs containing an abasic lesion and dGTP, dTTP, or dATP as the incoming nucleotide. The structures reveal a mechanism of translesion synthesis across an abasic lesion that differs from that in other Pols. Both the abasic lesion and the incoming dNTPs are intrahelical and are closely apposed across a constricted active site cleft. The dNTPs partake in distinct networks of hydrogen bonds in the "void" opposite the lesion. These different patterns of hydrogen bonds, as well as stacking interactions, may underlie Polι's small preference for insertion of dGTP over other nucleotides opposite this common lesion.

Original languageEnglish (US)
Pages (from-to)530-537
Number of pages8
JournalStructure
Volume17
Issue number4
DOIs
StatePublished - Apr 15 2009

Keywords

  • DNA
  • PROTEINS

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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