title: Micronuclei formation with chromosome breaks and gene amplification caused by Vpr, an accessory gene of human immunodeficiency virus.
abstract: Vpr, an accessory gene of human immunodeficiency virus, induces cell cycle abnormality by accumulating cells at the G2-M phase. We reported recently that Vpr caused both micronuclei formation and aneuploidy. Here, we show that Vpr also induced chromosome breaks and gene amplification. Expression of Vpr induced more than 10-fold increase of colonies resistant to N-(phosphonacetyl)-L-aspartate, an inhibitor of pyrimidine de novo synthesis. Fluorescence in situ hybridization analysis detected that 4 of 10 N-(phosphonacetyl)-L-aspartate resistant clones studied had intrachromosomal amplification of carbamyl-phosphate synthetase/aspartate transcarbamoylase/dihydroorotase gene. Another single clone had dicentrics. Data suggested that the Vpr-induced chromosome breaks leading to gene amplification, followed by bridge-breakage-fusion cycle, were one of the possible mechanisms of Vpr-induced genomic instability.
authors.affiliation: Department of Intractable Diseases, International Medical Center of Japan, Tokyo.
authors.forename: M
authors.initials: M
authors.lastname: Shimura
authors.forename: Y
authors.initials: Y
authors.lastname: Onozuka
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: K
authors.initials: K
authors.lastname: Hatake
authors.forename: F
authors.initials: F
authors.lastname: Takaku
authors.forename: Y
authors.initials: Y
authors.lastname: Ishizaka
mesh_terms: D000782:Aneuploidy; D001221:Aspartate Carbamoyltransferase / Q000235:genetics*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D004080:Dihydroorotase / Q000235:genetics*; D005354:Fibrosarcoma / Q000473:pathology; D016195:G2 Phase; D005784:Gene Amplification; D016336:Gene Products, vpr / Q000502:physiology*; D016334:Genes, vpr; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D048629:Micronuclei, Chromosome-Defective; D009097:Multienzyme Complexes / Q000235:genetics*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D054325:vpr Gene Products, Human Immunodeficiency Virus
chemical_list: C033626:CAD trifunctional enzyme; D016336:Gene Products, vpr; D009097:Multienzyme Complexes; D054325:vpr Gene Products, Human Immunodeficiency Virus; D001224:Aspartic Acid; C013195:sparfosic acid; D001221:Aspartate Carbamoyltransferase; D004080:Dihydroorotase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing); D010746:Phosphonoacetic Acid