Nucleic Acids Research, Vol 26, Issue 12 2917-2922, Copyright © 1998 by Oxford University Press
M Takao, H Aburatani, K Kobayashi and A Yasui
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.
ARTICLES
Mitochondrial targeting of human DNA glycosylases for repair of oxidative DNA damage
Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-77, Japan.
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|
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