Nucleic Acids Research, Vol 26, Issue 20 4611-4617, Copyright © 1998 by Oxford University Press
M Otterlei, T Haug, TA Nagelhus, G Slupphaug, T Lindmo and HE Krokan
Nuclear (UNG2) and mitochondrial (UNG1) forms of human uracil-DNA
glycosylase are both encoded by the UNG gene but have different N- terminal
sequences. We have expressed fusion constructs of truncated or site-mutated
UNG cDNAs and green fluorescent protein cDNA and studied subcellular
sorting. The unique 44 N-terminal amino acids in UNG2 are required, but not
sufficient, for complete sorting to nuclei. In this part the motif
R17K18R19is essential for sorting. The complete nuclear localization signal
(NLS) in addition requires residues common to UNG2 and UNG1 within the 151
N-terminal residues. Replacement of certain basic residues within this
region changed the pattern of subnuclear distribution of UNG2. The 35
unique N-terminal residues in UNG1 constitute a strong and complete
mitochondrial localization signal (MLS) which when placed at the N-terminus
of UNG2 overrides the NLS. Residues 11-28 in UNG1 have the potential of
forming an amphiphilic helix typical of MLSs and residues 1-28 are
essential and sufficient for mitochondrial import. These results
demonstrate that UNG1 contains a classical and very strong MLS, whereas
UNG2 contains an unusually long and complex NLS, as well as subnuclear
targeting signals in the region common to UNG2 and UNG1.
ARTICLES
Nuclear and mitochondrial splice forms of human uracil-DNA glycosylase contain a complex nuclear localisation signal and a strong classical mitochondrial localisation signal, respectively
Institute of Cancer Research and Molecular Biology and Department of Physics, Norwegian University of Science and Technology, N-7005 Trondheim, Norway.
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