Implication of Mammalian Ribosomal Protein S3 in the Processing of DNA Damage

Abstract

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.

Translocation of human ribosomal protein S3 to sites of DNA damage is dependant on ERK-mediated phosphorylation following genotoxic stress

“…While the hS3 is associated with ribosomal functions [21][22][23], it is also involved with BER [7,10,11,15,24,25]. We therefore tested whether agents that damage DNA could result in hS3 moving from its primary location in the cytoplasm to the nucleus where it would be poised to interact with DNA.…”

Ribosomal Proteins and Colorectal Cancer

“…The Minute drosophila, the viable but abnormal phenotypes models of RP genes mutation, strongly demonstrated the extraribosomal functions of RP49, RPL9 and RPS13. Another powerful illustration is RPS3 which has endonuclease activity and could be used for DNA repair, [41] and also activate caspase 8 and caspase 3 to induce cell apoptosis. The dual-function was performed by its different domains [42].…”

An Oxidative Damage-specific Endonuclease from Rat Liver Mitochondria

“…Unlike mtODE, the S3 protein was reported to cleave at FapyG adducts (46). It should be noted that the human ribosomal S3 protein has not been shown to process 8-oxoG or FapyG adducts (47). 2 mtODE is separable from the major endonuclease previously identified in mitochondria, mitochondrial endonuclease G (48).…”