Molecular cloning and characterization of the human KIN17 cDNA encoding a component of the UVC response that is conserved among metazoans

We describe the cloning and characterization of the human KIN17 cDNA encodi ng a 45 kDa zinc finger nuclear protein. Previous reports indicated that mo use kin17 protein may play a role in illegitimate recombination and in gene regulation, Furthermore, overproduction of mouse kin17 protein inhibits th e growth of mammalian cells, particularly the proliferation of human tumour -derived cells. We show here that the KIN17 gene is remarkably conserved du ring evolution. Indeed, the human and mouse kin17 proteins are 92.4% identi cal. Furthermore, DNA sequences from fruit fly and filaria code for protein s that are 60% identical to the mammalian kin17 proteins, indicating conser vation of the KIN17 gene among metazoans, The human KIN17 gene, named (HSA) KIN17, is located on human chromosome 10 at p15-p14, The (HSA)KIN17 RNA is ubiquitously expressed in all the tissues and organs examined, although mus cle, heart and testis display the highest levels. UVC irradiation of quiesc ent human primary fibroblasts increases (HSA)KIN17 RNA with kinetics simila r to those observed in mouse cells, suggesting that up-regulation of the (H SA)KIN17 gene after UVC irradiation is a conserved response in mammalian ce lls. (HSA)kin17 protein is concentrated in intranuclear focal structures in proliferating cells as judged by indirect immunofluorescence. UVC irradiat ion disassembles (HSA)kin17 foci in cycling cells, indicating a link betwee n the intranuclear distribution of (HSA)kin17 protein and the DNA damage re sponse.