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  • Title: Micronuclei formation with chromosome breaks and gene amplification caused by Vpr, an accessory gene of human immunodeficiency virus.
    Author: Shimura M, Onozuka Y, Yamaguchi T, Hatake K, Takaku F, Ishizaka Y.
    Journal: Cancer Res; 1999 May 15; 59(10):2259-64. PubMed ID: 10344725.
    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.
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