p53 tumor suppressor protein plays a key role in maintaining genomic integrity and regulating growth control following exposure to DNA-damaging agents. Moreover, it is likely to control genome stability by affecting homologous recombination. p53 can work as a transcription factor in Sacharomyces cerevisiae, therefore this organism represents a good genetic model in which to investigate the molecular mechanism and genetic control of DNA damage-induced recombination. We expressed wild-type human p53 and a mutated form lacking transcriptional activity in S.cerevisiae strain RS112, which carries a synthetic intrachromosomal recombination substrate, and the frequencies of spontaneous and DNA damage-induced homologous recombination were determined. While an increase in intrachromosomal recombination induced by both UV radiation and methylmethane sulphonate (MMS) was observed in yeast cells carrying the void plasmid, p53 expression significantly reduced recombination frequency. The mutated p53 significantly reduced UV-induced recombination but had no effect on MMS-induced recombination. Our results suggest that human p53 inhibits homologous recombination induced by UV and MMS by mechanisms involving stabilization and/or phosphorylation of the protein
Involvement of human p53 in induced intrachromosomal recombination in Saccharomyces cerevisiae
R Del Carratore;
2004
Abstract
p53 tumor suppressor protein plays a key role in maintaining genomic integrity and regulating growth control following exposure to DNA-damaging agents. Moreover, it is likely to control genome stability by affecting homologous recombination. p53 can work as a transcription factor in Sacharomyces cerevisiae, therefore this organism represents a good genetic model in which to investigate the molecular mechanism and genetic control of DNA damage-induced recombination. We expressed wild-type human p53 and a mutated form lacking transcriptional activity in S.cerevisiae strain RS112, which carries a synthetic intrachromosomal recombination substrate, and the frequencies of spontaneous and DNA damage-induced homologous recombination were determined. While an increase in intrachromosomal recombination induced by both UV radiation and methylmethane sulphonate (MMS) was observed in yeast cells carrying the void plasmid, p53 expression significantly reduced recombination frequency. The mutated p53 significantly reduced UV-induced recombination but had no effect on MMS-induced recombination. Our results suggest that human p53 inhibits homologous recombination induced by UV and MMS by mechanisms involving stabilization and/or phosphorylation of the proteinI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
