Article,
Minimum Criteria for DNA Damage-Induced Phase Advances in Circadian Rhythms
PLoS Comput Biol, 5 (5): e1000384+ (May 2009)
DOI: 10.1371/journal.pcbi.1000384
Abstract
<title>Author Summary</title> <p>Molecular components and mechanisms that connect cell cycle and circadian rhythms are important for the well-being of an organism. Cell cycle machinery regulates the progress of cell growth and division while the circadian rhythm network generates an ∼24 h time-keeping mechanism that regulates the daily processes of an organism (i.e. metabolism, bowel movements, body temperature, etc.). It is observed that cell divisions usually occur during a certain time window of a day, which indicated that there are circadian-gated cell divisions. Moreover, it's been shown that mice are more prone to develop cancer when certain clock genes are mutated resulting in an arrhythmic clock. Recently, a cell cycle checkpoint regulator, Chk2, was identified as a component that influences a core clock component and creates mostly phase advances (i.e., jet lags due to traveling east) in circadian rhythms upon DNA damage. This phase response with minimum delays is an unexpected result, and the molecular mechanism behind this phenomenon remains unknown. Our computational analyses of a mathematical model reveal two molecular criteria that account for the experimentally observed phase responses of the circadian clock upon DNA damage. These results demonstrate how circadian clock regulation by cell cycle checkpoint controllers provides another layer of complexity for efficient DNA damage responses.</p>
