The abasic (AP) sites, the major mutagenic and cytotoxic genomic lesions, induced directly by oxidative stress and indirectly after excision of damaged bases by DNA glycosylases, are repaired by AP-endonucleases (APEs). Among two APEs in Saccharomyces cerevisiae, Apn1 provides the major APE activity, and Apn2, the ortholog of the mammalian APE, provides back-up activity. We have cloned apn1 and apn2 genes of Schizosaccharomyces pombe, and have shown that inactivation of Apn2 and not Apn1 sensitizes this fission yeast to alkylation and oxidative damage-inducing agents, which is further enhanced by Apn1 inactivation. We also show that Uve1, present in S.pombe but not in S.cerevisiae, provides the back-up APE activity together with Apn1. We confirmed the presence of APE activity in recombinant Apn2 and in crude cell extracts. Thus S.pombe is distinct from S.cerevisiae, and is similar to mammalian cells in having Apn2 as the major APE.
|Number of pages||12|
|Journal||Nucleic Acids Research|
|State||Published - 2004|
Bibliographical noteFunding Information:
We thank Dr D. Konkel for careful editing of the manuscript, Drs V. Bashkirov, P. Doetsch, W. Heyer and M. Sipiczki for S.pombe strains, and Drs. S. Seki and K. Akiyama for the human APE1 and APE2 cDNA plasmids. This work was supported by USPHS grants R01 CA53791, ES08457 and P50 ES06676. B.R. is grateful to the Soros Foundation for a Fellowship award and to the Hungarian Science and Technology Foundation, for a travel grant.
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