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

Andrey G. Baranovskiy, Nigar D. Babayeva, Victoria G. Liston, Igor B. Rogozin, Eugene V. Koonin, Youri I. Pavlov, Dmitry G. Vassylyev, Tahir H. Tahirov

Research output: Contribution to journalArticle

60 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3026-3036
Number of pages11
JournalCell Cycle
Volume7
Issue number19
DOIs
StatePublished - Oct 1 2008

Keywords

  • DNA polymerase δ
  • Human
  • Myb
  • OB
  • P50
  • P66
  • Phosphodiesterase
  • Pol δ
  • Pol31
  • Pol32
  • Yeast

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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    Baranovskiy, A. G., Babayeva, N. D., Liston, V. G., Rogozin, I. B., Koonin, E. V., Pavlov, Y. I., Vassylyev, D. G., & Tahirov, T. H. (2008). X-ray structure of the complex of regulatory subunits of human DNA polymerase δ. Cell Cycle, 7(19), 3026-3036. https://doi.org/10.4161/cc.7.19.6720