Disruption of p53 by the viral oncoprotein HPV16-E6 does not deregulate chromosomal homologous recombination in a transcriptional interference-free assay system.
In addition to its well established role in the maintenance of genome integrity by regulating transcription of genes involved in cell cycle arrest and programmed cell death, the tumour suppressor p53 has also been shown to inhibit spontaneous chromosomal homologous recombination (HR) between adjacent transcription units, raising the possibility that p53 may prevent chromosomal rearrangements by suppressing HR between repetitive DNA elements (ectopic HR). Consistent with its role in the maintenance of genome integrity is that p53 does not suppress HR between homologous chromosomes (allelic HR) or identical sister chromatids, raising the question of how p53 discriminates between ectopic and allelic HR events. Here, we report that disruption of human p53 by the viral oncoprotein HPV16-E6 does not result in increased rates of chromosomal HR between adjacent DNA repeats in a transcriptional interference-free assay system in which a HR reporter gene can escape transcription repression. These results argue against a direct role for p53 in the regulation of HR mechanisms, imply that HR assay systems may be important determinants of the outcome, and suggest that p53 may suppress ectopic HR through its known ability to repress transcription and alter chromatin structure.
Lemelin
Jean-François
JF
Université de Montréal, Montréal, Quebec, Canada.
Abaji
Christine
C
Cousineau
Isabelle
I
Belmaaza
Abdellah
A
D000123:Acetyltransferases / Q000378:metabolism; D001681:Biological Assay / Q000379:methods*; D002478:Cells, Cultured; D002877:Chromosomes, Human / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005785:Gene Conversion; D017353:Gene Deletion; D016678:Genome / Q000235:genetics; D045325:HCT116 Cells; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D004247:DNA; D000123:Acetyltransferases; C045336:puromycin N-acetyltransferase