Micronuclei formation with chromosome breaks and gene amplification caused by Vpr, an accessory gene of human immunodeficiency virus.
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.
Shimura
M
M
Department of Intractable Diseases, International Medical Center of Japan, Tokyo.
Onozuka
Y
Y
Yamaguchi
T
T
Hatake
K
K
Takaku
F
F
Ishizaka
Y
Y
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
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