A human apurinic/apyrimidinic
endonuclease activity, called
AP endonuclease I, is missing from or altered specifically in cells cultured from
Xeroderma pigmentosum group-D individuals (XP-D cells) (Kuhnlein, U., Lee, B., Penhoet, E. E., and Linn, S. (1978)
Nucleic Acids Res. 5,951-960). We have now observed that another nuclease activity,
UV endonuclease III, is similarly not detected in XP-D cells and is inseparable from the
AP endonuclease I activity. This activity preferentially cleaves the phosphodiester backbone of heavily ultraviolet-irradiated
DNA at unknown lesions as well as at one of the phosphodiester bonds within a
cyclobutane pyrimidine dimer. The nuclease activities have been purified from mouse cells to yield a
peptide of M(r) = 32,000, whose sequence indicates identity with
ribosomal protein S3. The nuclease activities all cross-react with immunopurified antibody directed against authentic rat
ribosomal protein S3, and, upon expression in Escherichia coli of a cloned rat
cDNA for
ribosomal protein S3, each of the activities was recovered and was indistinguishable from those of the mammalian
UV endonuclease III. Moreover, the
protein expressed in E. coli and its activities cross-react with the rat
protein antibody.
Ribosomal protein S3 contains a potential
nuclear localization signal, and the
protein isolated as a nuclease also has a glycosylation pattern consistent with a nuclear localization as determined by
lectin binding. The unexpected role of a
ribosomal protein in DNA damage processing and the unexplained inability to detect the nuclease activities in extracts from XP-D cells are discussed.