Structure of the catalytic core of S. cerevisiae DNA polymerase eta: implications for translesion DNA synthesis

Mol Cell. 2001 Aug;8(2):417-26. doi: 10.1016/s1097-2765(01)00306-9.

Abstract

DNA polymerase eta is unique among eukaryotic polymerases in its proficient ability to replicate through a variety of distorting DNA lesions. We report here the crystal structure of the catalytic core of S. cerevisiae DNA polymerase eta, determined at 2.25A resolution. The structure reveals a novel polydactyl right hand-shaped molecule with a unique polymerase-associated domain. We identify the catalytic residues and show that the fingers and thumb domains are unusually small and stubby. In particular, the unexpected absence of helices "O" and "O1" in the fingers domain suggests that openness of the active site is the critical feature which enables DNA polymerase eta to replicate through DNA lesions such as a UV-induced cis-syn thymine-thymine dimer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Binding Sites
  • Catalysis
  • Catalytic Domain
  • Crystallography, X-Ray
  • DNA Damage
  • DNA Repair*
  • DNA Replication*
  • DNA-Directed DNA Polymerase / chemistry*
  • DNA-Directed DNA Polymerase / metabolism
  • Genes, Reporter / genetics
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Structure, Tertiary*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / enzymology*
  • Sequence Alignment
  • Templates, Genetic
  • Xeroderma Pigmentosum / genetics

Substances

  • Recombinant Fusion Proteins
  • DNA-Directed DNA Polymerase
  • Rad30 protein

Associated data

  • PDB/1JIH