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Archaeal DNA uracil repair via direct strand incision: A minimal system reconstituted from purified components

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Author(s)

  • Lars Schomacher
  • K. Anke Schuerer
  • Elena Ciirdaeva
  • Paul McDermott
  • James P. J. Chong
  • Wilfried Kramer
  • Hans-Joachim Fritz

Department/unit(s)

Publication details

JournalMutation research-Dna repair
DatePublished - 4 Apr 2010
Issue number4
Volume9
Number of pages10
Pages (from-to)438-447
Original languageEnglish

Abstract

Hydrolytic deamination of DNA cytosine residues results in U/G mispairs, pre-mutagenic lesions threatening long-term genetic stability. Hence, DNA uracil repair is ubiquitous throughout all extant life forms and base excision repair, triggered by a uracil DNA glycosylase (UDG), is the mechanistic paradigm adopted, as it seems, by all bacteria and eukaryotes and a large fraction of archaea. However, members of the UDG superfamily of enzymes are absent from the extremely thermophilic archaeon Methanothermobacter thermautotrophicus Delta H. This organism, as a hitherto unique case, initiates repair by direct strand incision next to the DNA-U residue, a reaction catalyzed by the DNA uridine endonuclease Mth212, an ExoIII homologue. To elucidate the detailed mechanism, in particular to identify the molecular partners contributing to this repair process, we reconstituted DNA uracil repair in vitro from only four purified enzymes of M. thermautotrophicus Delta H. After incision at the 5'-side of a 2'-d-uridine residue by Mth212 DNA polymerase B (mthPolB) is able to take over the 3'-OH terminus and carry out repair synthesis generating a 5'-flap structure that is resolved by mthFEN, a 5'-flap endonuclease. Finally. DNA ligase seals the resulting nick. This defines mechanism and minimal enzymatic requirements of DNA-U repair in this organism. (C) 2010 Elsevier B.V. All rights reserved.

    Research areas

  • Hydrolytic deamination, DNA uracil repair, Strand incision repair, DNA uridine endonuclease, Thermophilic archaea, Methanothermobacter thermautotrophicus, Delta H, THERMOAUTOTROPHICUM DELTA-H, BASE EXCISION-REPAIR, EXOIII HOMOLOG MTH212, METHANOBACTERIUM-THERMOAUTOTROPHICUM, INORGANIC PYROPHOSPHATASE, COMPLETE GENOME, POLYMERASE, PROTEINS, GLYCOSYLASE, REPLICATION

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