 |
Journal articles
Mutant p53 proteins stimulate spontaneous and radiation-induced intrachromosomal homologous recombination independently of the alteration of the transactivation activity and of the G1 checkpoint
Abstract : We report here a systematic analysis of the eects of dierent p53 mutations on both spontaneous and radiation-stimulated homologous recombination in mouse L cells. In order to monitor dierent recombination pathways, we used both direct and inverted repeat recombination substrates. In each line bearing one of these substrates, we expressed p53 proteins mutated at positions: 175, 248 or 273. p53 mutations leading to an increased spontaneous recombination rate also stimulate radiation-induced recombination. The eect on recombi-nation may be partially related to the conformation of the p53 protein. Moreover, p53 mutations act on recombination between direct repeats as well as between inverted repeats indicating that strand invasion mechanisms are stimulated. Although all of the p53 mutations aect the p53 transactivation activity measured on the WAF1 and MDM2 gene promoters, no correlation between the transactivation activity and the extent of homologous recombination can be drawn. Finally, some p53 mutations do not aect the G1 arrest after radiation but stimulate radiation-induced recombination. These results show that the role of p53 on transactivation and G1 cell cycle checkpoint is separable from its involvement in homologous recombination. A direct participation of p53 in the recombination mechanism itself is discussed.
https://hal-cea.archives-ouvertes.fr/cea-01938157
Contributor : Yannick Saintigny Connect in order to contact the contributor
Submitted on : Wednesday, November 28, 2018 - 2:49:28 PM
Last modification on : Tuesday, October 19, 2021 - 11:00:25 AM
Contributor : Yannick Saintigny Connect in order to contact the contributor
Submitted on : Wednesday, November 28, 2018 - 2:49:28 PM
Last modification on : Tuesday, October 19, 2021 - 11:00:25 AM
File
Oncogene_p53.pdf
Publisher files allowed on an open archive