X-ray structure of the complex of regulatory subunits of human DNA polymerase δ

Academic Article

Abstract

  • The eukaryotic DNA polymerase δ (Pol δ) participates in genome replication, homologous recombination, DNA repair and damage tolerance. Regulation of the plethora of Pol δ functions depends on the interaction between the second (p50) and third (p66) non-catalytic subunits. We report the crystal structure of p50•p66N complex featuring oligonucleotide binding and phosphodiesterase domains in p50 and winged helix-turn-helix N-terminal domain in p66. Disruption of the interaction between the yeast orthologs of p50 and p66 by strategic amino acid changes leads to cold-sensitivity, sensitivity to hydroxyurea and to reduced UV mutagenesis, mimicking the phenotypes of strains where the third subunit of Pol δ is absent. The second subunits of all B family replicative DNA polymerases in archaea and eukaryotes, except Pol δ, share a three-domain structure similar to p50•p66N, raising the possibility that a portion of the gene encoding p66 was derived from the second subunit gene relatively late in evolution. ©2008 Landes Bioscience.
  • Published In

  • Cell Cycle  Journal
  • Digital Object Identifier (doi)

    Author List

  • Baranovskiy AG; Babayeva ND; Liston VG; Rogozin IB; Koonin EV; Pavlov YI; Vassylyev DG; Tahirov TH
  • Start Page

  • 3026
  • End Page

  • 3036
  • Volume

  • 7
  • Issue

  • 19