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 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. (HSA)kin17 protein is concentrated in intranuclear focal structures in proliferating cells as judged by indirect immunofluorescence. UVC irradiation disassembles (HSA)kin17 foci in cycling cells, indicating a link between the intranuclear distribution of (HSA)kin17 protein and the DNA damage response.
Kannouche
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P
Laboratoire de Génétique de la Radiosensibilité, Département de Radiobiologie et de Radiopathologie, Direction des Sciences du Vivant, Centre d'Etudes de Fontenay-aux-Roses, CEA, 92265 Fontenay-aux-Roses, France.
Mauffrey
P
P
Pinon-Lataillade
G
G
Mattei
M G
MG
Sarasin
A
A
Daya-Grosjean
L
L
Angulo
J F
JF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017178:Brugia malayi / Q000235:genetics; D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004249:DNA Damage; D018076:DNA, Complementary / Q000235:genetics* / Q000528:radiation effects*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics; D019143:Evolution, Molecular; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D012313:RNA / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D016601:RNA-Binding Proteins; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D016335:Zinc Fingers / Q000235:genetics* / Q000528:radiation effects
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C489487:KIN protein, human; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C071214:Kin protein, mouse; D012313:RNA