DNA synthesis across an abasic lesion by human DNA polymerase iota

Structure. 2009 Apr 15;17(4):530-7. doi: 10.1016/j.str.2009.02.015.

Abstract

Abasic sites are among the most abundant DNA lesions formed in human cells, and they present a strong block to replication. DNA polymerase iota (Poliota) 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 Poliota 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 Poliota's small preference for insertion of dGTP over other nucleotides opposite this common lesion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding Sites
  • Catalysis
  • Crystallography, X-Ray
  • DNA / chemistry
  • DNA / genetics
  • DNA Damage*
  • DNA Repair*
  • DNA Replication*
  • DNA-Directed DNA Polymerase / chemistry
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism*
  • Deoxyadenine Nucleotides / chemistry
  • Deoxyguanine Nucleotides / chemistry
  • Humans
  • Hydrogen Bonding
  • Kinetics
  • Models, Molecular
  • Nucleic Acid Conformation
  • Nucleotides / chemistry
  • Nucleotides / genetics
  • Protein Binding
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism

Substances

  • Deoxyadenine Nucleotides
  • Deoxyguanine Nucleotides
  • Nucleotides
  • Recombinant Fusion Proteins
  • deoxyguanosine triphosphate
  • DNA
  • DNA polymerase iota
  • DNA-Directed DNA Polymerase
  • 2'-deoxyadenosine triphosphate