Overexpression of kin17 protein disrupts nuclear morphology and inhibits the growth of mammalian cells.
UVC or ionizing radiation of mammalian cells elicits a complex genetic response that allows recovery and cell survival. Kin17 gene, which is highly conserved among mammals, is upregulated during this response. Kin17 gene encodes a 45 kDa protein which binds to DNA and presents a limited similarity with a functional domain of the bacterial RecA protein. Kin17 protein is accumulated in the nucleus of proliferating fibroblasts and forms intranuclear foci. Using expression vectors, we show that overexpression of kin17 protein inhibits cell-cycle progression into S phase. Our results indicate that growth inhibition correlates with disruption of the nuclear morphology which seems to modify the intranuclear network required during the early steps of DNA replication. We report that a mutant encoding a protein deleted from the central domain of kin17 protein enhanced these effects whereas the deletion of the C-terminal domain considerably reduced them. These mutants will be used to elucidate the molecular mechanism by which kin17 protein alters cell growth and DNA replication.
Kannouche
P
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, avenue du Général-Leclerc, B.P. no. 6, France.
Angulo
J F
JF
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D001973:Bromodeoxyuridine / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung; D002455:Cell Division / Q000235:genetics; D002467:Cell Nucleus / Q000737:chemistry / Q000235:genetics*; D002843:Chromatin / Q000235:genetics; D004261:DNA Replication / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005111:Extrachromosomal Inheritance; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D005799:Genes, Dominant; D006367:HeLa Cells; D006801:Humans; D008175:Lung Neoplasms; D008322:Mammals; D016296:Mutagenesis / Q000502:physiology; D009687:Nuclear Proteins; D009690:Nucleic Acid Conformation; D016601:RNA-Binding Proteins; D011938:Rec A Recombinases / Q000235:genetics; D016196:S Phase / Q000235:genetics; D016335:Zinc Fingers / Q000235:genetics
D000952:Antigens, Polyomavirus Transforming; D002843:Chromatin; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C489487:KIN protein, human; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D011938:Rec A Recombinases; D001973:Bromodeoxyuridine