Journal Article

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

Patricia Kannouche, Philippe Mauffrey, Ghislaine Pinon-Lataillade, Marie Geneviève Mattei, Alain Sarasin, Leela Daya-Grosjean and Jaime F. Angulo

in Carcinogenesis

Volume 21, issue 9, pages 1701-1710
Published in print September 2000 | ISSN: 0143-3334
Published online September 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.9.1701
Molecular cloning and characterization of the human KIN17 cDNA encoding a component of the UVC response that is conserved among metazoans

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We describe the cloning and characterization of the human KIN17 cDNA encoding a 45 kDa zinc finger nuclear protein. Previous reports indicated that mouse kin17 protein may play a role in illegitimate recombination and in gene regulation. Furthermore, overproduction of mouse kin17 protein inhibits the growth of mammalian cells, particularly the proliferation of human tumour-derived cells. We show here that the KIN17 gene is remarkably conserved during evolution. Indeed, the human and mouse kin17 proteins are 92.4% identical. Furthermore, DNA sequences from fruit fly and filaria code for proteins that are 60% identical to the mammalian kin17 proteins, indicating conservation 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 muscle, heart and testis display the highest levels. UVC irradiation of quiescent human primary fibroblasts increases (HSA)KIN17 RNA with kinetics similar to those observed in mouse cells, suggesting that up-regulation of the (HSA)KIN17 gene after UVC irradiation is a conserved response in mammalian cells. HSAkin17 protein is concentrated in intranuclear focal structures in proliferating cells as judged by indirect immunofluorescence. UVC irradiation disassembles HSAkin17 foci in cycling cells, indicating a link between the intranuclear distribution of HSAkin17 protein and the DNA damage response.

Keywords: BSA, bovine serum albumin; DMEM, Dulbecco's modified Eagle's medium; FCS, foetal calf serum; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; IIF, indirect immunofluorescence; MEM, minimum Eagle's medium; NLS, nuclear localization signal; PBS, phosphate-buffered saline; 3′-UTR, 3′-untranslated region; 5′-UTR, 5′-untranslated region.

Journal Article.  7181 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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