Nucleic Acids Research, Vol 26, Issue 21 4953-4959, Copyright © 1998 by Oxford University Press
S Bharati, HE Krokan, L Kristiansen, M Otterlei and G Slupphaug
The preform of human mitochondrial uracil-DNA glycosylase (UNG1) contains
35 N-terminal residues required for mitochondrial targeting. We have
examined processing of human UNG1 expressed in insect cells and processing
in vitro by human mitochondrial extracts . In insect cells we detected a
major processed form lacking 29 of the 35 unique N- terminal residues
(UNG1Delta29, 31 kDa) and two minor forms lacking the 75 and 77 N-terminal
residues, respectively (UNG1Delta75 and UNG1Delta77, 26 kDa). Purified
UNG1Delta29 was effectively cleaved in vitro to a fully active 26 kDa form
by human mitochondrial extracts. Furthermore, endogenous forms of 31 and 26
kDa were also observed in HeLa mitochondrial extracts. The sequences at the
cleavage sites, as identified by peptide sequencing, were compatible with
the known specificity of mitochondrial processing peptidase (MPP). However,
in vitro cleavage of UNG1Delta29 by mitochondrial extracts did not require
divalent cations and was stimulated by EDTA, indicating the involvement of
a processing peptidase distinct from MPP at the second site. Interestingly,
while UNG1Delta29 generally has the typical properties reported for other
uracil-DNA glycosylases, it is not inhibited by apurinic/apyrimidinic
sites. Our results indicate that the preform of human mitochondrial
uracil-DNA glycosylase is processed to distinctly different forms lacking
29 or 75/77 N-terminal residues, respectively.
ARTICLES
Human mitochondrial uracil-DNA glycosylase preform (UNG1) is processed to two forms one of which is resistant to inhibition by AP sites
Institute for Cancer Research and Molecular Biology, Norwegian University of Science and Technology, N-7005 Trondheim, Norway.
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