Loss of cryptochrome reduces cancer risk in p53 mutant mice

Nuri Ozturk; Jin Hyup Lee; Shobhan Gaddameedhi; Aziz Sancar

doi:10.1073/pnas.0813028106

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Loss of cryptochrome reduces cancer risk in p53 mutant mice

Journal article

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Loss of cryptochrome reduces cancer risk in p53 mutant mice

Nuri Ozturk, Jin Hyup Lee, Shobhan Gaddameedhi and Aziz Sancar

Proceedings of the National Academy of Sciences - PNAS, Vol.106(8), pp.2841-2846

02/24/2009

DOI: https://doi.org/10.1073/pnas.0813028106

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https://hdl.handle.net/2376/104163

PMCID: PMC2634797

PMID: 19188586

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Abstract

Biological Sciences

apoptosis

circadian clock

DNA repair

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 the Cryptochrome ( 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 the Cry mutation on carcinogenesis in a mouse strain prone to cancer because of a p53 mutation, with the expectation that clock disruption in this sensitized background would further increase cancer risk. Paradoxically, we find that the Cry mutation protects p53 mutant mice from the early onset of cancer and extends their median lifespan ≈50%, in part by sensitizing p53 mutant cells to apoptosis in response to genotoxic stress. These results suggest alternative therapeutic approaches in management of cancers associated with a p53 mutation.

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Title: Loss of cryptochrome reduces cancer risk in p53 mutant mice
Creators: Nuri Ozturk - Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599
Jin Hyup Lee - Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599
Shobhan Gaddameedhi - Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599
Aziz Sancar - Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.106(8), pp.2841-2846
Academic Unit: UNKNOWN
Publisher: National Academy of Sciences
Identifiers: 99900547087401842
Language: English
Resource Type: Journal article