A novel interaction between DNA ligase III and DNA polymerase γ plays an essential role in mitochondrial DNA stability

Ananya De, Colin R Campbell

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The data in the present study show that DNA polymerase γ and DNA ligase III interact in mitochondrial protein extracts from cultured HT1080 cells. An interaction was also observed between the two recombinant proteins in vitro. Expression of catalytically inert versions of DNA ligase III that bind DNA polymerase γ was associated with reduced mitochondrial DNA copy number and integrity. In contrast, overexpression of wild-type DNA ligase III had no effect on mitochondrial DNA copy number or integrity. Experiments revealed that wild-type DNA ligase III facilitates the interaction of DNA polymerase γ with a nicked DNA substrate in vitro, and that the zinc finger domain of DNA ligase III is required for this activity. Mitochondrial protein extracts prepared from cells overexpressing a DNA ligase III protein that lacked the zinc finger domain had reduced base excision repair activity compared with extracts from cells overexpressing the wild-type protein. These data support the interpretation that the interaction of DNA ligase III and DNA polymerase γ is required for proper maintenance of the mammalian mitochondrial genome.

Original languageEnglish (US)
Pages (from-to)175-186
Number of pages12
JournalBiochemical Journal
Volume402
Issue number1
DOIs
StatePublished - Feb 15 2007

Keywords

  • DNA integrity
  • DNA ligase III
  • DNA polymerase γ
  • HT1080
  • Mitochondria
  • Zinc finger domain

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