The family X DNA polymerase from Deinococcus radiodurans adopts a non-standard extended conformation

J Biol Chem. 2009 May 1;284(18):11992-9. doi: 10.1074/jbc.M809342200. Epub 2009 Feb 26.

Abstract

Deinococcus radiodurans is an extraordinarily radioresistant bacterium that is able to repair hundreds of radiation-induced double-stranded DNA breaks. One of the players in this pathway is an X family DNA polymerase (PolX(Dr)). Deletion of PolX(Dr) has been shown to decrease the rate of repair of double-stranded DNA breaks and increase cell sensitivity to gamma-rays. A 3'-->5' exonuclease activity that stops cutting close to DNA loops has also been demonstrated. The present crystal structure of PolX(Dr) solved at 2.46-A resolution reveals that PolX(Dr) has a novel extended conformation in stark contrast to the closed "right hand" conformation commonly observed for DNA polymerases. This extended conformation is stabilized by the C-terminal PHP domain, whose putative nuclease active site is obstructed by its interaction with the polymerase domain. The overall conformation and the presence of non standard residues in the active site of the polymerase X domain makes PolX(Dr) the founding member of a novel class of polymerases involved in DNA repair but whose detailed mode of action still remains enigmatic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Crystallography, X-Ray
  • DNA Breaks, Double-Stranded / radiation effects
  • DNA Repair / radiation effects
  • DNA-Directed DNA Polymerase / chemistry*
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism
  • Deinococcus / enzymology*
  • Deinococcus / genetics
  • Gamma Rays
  • Gene Deletion
  • Protein Structure, Tertiary / physiology
  • Structure-Activity Relationship

Substances

  • Bacterial Proteins
  • DNA polymerase X
  • DNA-Directed DNA Polymerase

Associated data

  • PDB/2W9M