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J Biol Chem, Vol. 275, Issue 16, 11824-11828, April 21, 2000

Alternative Excision Repair Pathway of UV-damaged DNA in Schizosaccharomyces pombe Operates Both in Nucleus and in Mitochondria^*

Shinji Yasuhira and Akira Yasui

From the Institute of Development, Aging and Cancer, Tohoku University, Seiryomachi 4-1, Aoba-Ku, Sendai 980-8575, Japan

The fission yeast, Schizosaccharomyces pombe, possesses a UV-damaged DNA endonuclease-dependent excision repair (UVER) pathway in addition to nucleotide excision repair pathway for UV-induced DNA damage. We examined cyclobutane pyrimidine dimer removal from the myo2 locus on the nuclear genome and the coI locus on the mitochondrial genome by the two repair pathways. While nucleotide excision repair repairs damage only on the nuclear genome, UVER efficiently removes cyclobutane pyrimidine dimers on both nuclear and mitochondrial genomes. The ectopically expressed wild type UV-damaged DNA endonuclease was localized to both nucleus and mitochondria, while modifications of N-terminal methionine codons restricted its localization to either of two organelles, suggesting an alternative usage of multiple translation initiation sites for targeting the protein to different organelles. By introducing the same mutations into the chromosomal copy of the uvde⁺ gene, we selectively inactivated UVER in either the nucleus or the mitochondria. The results of UV survival experiments indicate that although UVER efficiently removes damage on the mitochondrial genome, UVER in the mitochondria hardly contributes to UV resistance of S. pombe cells. We suggest a possible UVER function in mitochondria as a backup system for other UV damage tolerance mechanisms.

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