Open AccessLoss of cryptochrome reduces cancer risk in p53 mutant mice
Author(s) -
Nuri Öztürk,
Jin Hyup Lee,
Shobhan Gaddameedhi,
Aziz Sancar
Publication year - 2009
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0813028106
Subject(s) - mutant , carcinogenesis , cryptochrome , cancer , mutation , cancer research , biology , circadian clock , genetics , apoptosis , circadian rhythm , endocrinology , gene
It is commonly thought that disruption of the circadian clock increases the cancer incidence in humans and mice. However, it was found that disruption of the clock by theCryptochrome (Cry ) mutation in mice did not increase cancer rate in the mutant mice even after exposing the animals to ionizing radiation. Therefore, in this study we tested the effect of theCry mutation on carcinogenesis in a mouse strain prone to cancer because of ap53 mutation, with the expectation that clock disruption in this sensitized background would further increase cancer risk. Paradoxically, we find that theCry mutation protectsp53 mutant mice from the early onset of cancer and extends their median lifespan ≈50%, in part by sensitizingp53 mutant cells to apoptosis in response to genotoxic stress. These results suggest alternative therapeutic approaches in management of cancers associated with ap53 mutation.