Mitochondrial targeting of human DNA glycosylases for repair of oxidative DNA damage

Masashi Takao, Hiroyuki Aburatani, Kumiko Kobayashi, Akira Yasui

Research output: Contribution to journalArticlepeer-review

226 Citations (Scopus)

Abstract

Oxidative damage to mitochondrial DNA has been implicated in human degenerative diseases and aging. Although removal of oxidative lesions from mitochondrial DNA occurs, the responsible DNA repair enzymes are poorly understood. By expressing the epitope-tagged proteins in COS-7 cells, we examined subcellular localizations of gene products of human DNA glycosylases: hOGG1, hMYH and hNTH1. A gene encoding for hOGG1 which excises 7,8-dihydro-8-oxoguanine (8-oxoG) from DNA generates four isoforms by alternative splicing (types 1a, 1b, 1c and 2). Three tagged isoforms (types 1b, 1c and 2) were localized in the mitochondria. Type 1a protein, which exclusively contains a putative nuclear localization signal, was sorted to the nucleus and lesser amount to the mitochondria. hMYH, a human homolog gene product of Escherichia coli mutY was mainly transported into the mitochondria. hNTH1 protein excising several pyrimidine lesions was transported into both the nucleus and mitochondria. In contrast to the three DNA glycosylases, translocation of the human major AP endonuclease (hAPE) into the mitochondria was hardly observed in COS-7 cells. These results suggest that the previously observed removal of oxidative base lesions in mitochondrial DNA is initiated by the above DNA glycosylases.

Original languageEnglish
Pages (from-to)2917-2922
Number of pages6
JournalNucleic acids research
Volume26
Issue number12
DOIs
Publication statusPublished - 1998 Jun 15

ASJC Scopus subject areas

  • Genetics

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