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A phylogenetically conserved DNA damage response resets the circadian clock.
Joshua J Gamsby1, Jennifer J Loros, Jay C Dunlap
1Department of Genetics, Dartmouth Medical School, Hanover, New Hampshire 03755-3844, USA.
Journal of Biological Rhythms
|May 26, 2009
Summary
DNA damage resets the mammalian circadian clock by altering key protein levels, similar to findings in fungi. This conserved response impacts biological timing and gene expression.
Area of Science:
- Chronobiology
- Molecular Biology
- Genetics
Background:
- The circadian clock regulates essential biological processes, influenced by environmental cues like light.
- Posttranslational modifications of core clock components mediate environmental influences.
- Previous research indicated DNA damage resets the circadian clock in fungi (Neurospora crassa).
Purpose of the Study:
- To investigate if DNA damage similarly affects the mammalian circadian clock.
- To explore the molecular mechanisms underlying DNA damage-induced circadian clock resetting in mammals.
Main Methods:
- Utilized mouse embryonic fibroblasts (PER2::LUC) and NIH3T3 cells.
- Induced DNA damage using methyl methane sulfonate and UV irradiation.
- Monitored circadian clock function via luciferase reporter assays and promoter activity.
Main Results:
- DNA damage induced phase advances in the mammalian circadian clock.
- Observed PER2 degradation, indicated by decreased luciferase signal.
- Demonstrated enhanced BMAL1 promoter activity during DNA damage.
Conclusions:
- DNA damage elicits conserved responses in the circadian clock from fungi to mammals.
- The findings highlight a link between DNA damage response pathways and circadian clock regulation.
- This conserved mechanism suggests a fundamental biological interplay between DNA integrity and cellular timing.
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