In the article “Circadian Clock, Cancer, and Chemotherapy,” the authors discuss the relationship between the circadian clock, cell cycle, DNA repair, and apoptosis. The authors then relate these relationships to cancer and treatment of cancer. The article backs their claims with numerous studies performed on both animal and human subjects. It also describes the importance of circadian rhythm in timing of drug delivery for cancer patients. This treatment method has been given the name chronotherapy and is successfully used today for the treatment of several other conditions. [1]
The article first discusses circadian clock regulation of DNA repair. It has only recently been discovered that the circadian clock is important in regulation of DNA …show more content…
Particularly, the clock has been tied to DNA damage repair checkpoint pathways. The ATR-Chk1 and ATM-Chk2 DNA damage signaling systems have both been tied to the circadian clock. The authors explain in detail how one must be cautioned against relying on data from tissue culture experiments. An example is given of an experiment that found mutations in the clock genes CLOCK, BMAL1, CRYs, and PERs had no effect on DNA repair pathways that were tested. Although, other experimental results show that at the level of an organism DNA repair pathways are effected and therefore circadian-controlled. The control mechanism is lost or overridden by homeostatic mechanisms in the tissue cultures. …show more content…
Apoptosis can be activated by sufficient DNA damage in cells, but the author puts it into its own specific relation to the clock. The circadian clock has recently been connected to both intrinsic and extrinsic apoptosis. The gene p53 is generally the dominant effector in promoting apoptosis in response to damaged DNA. However, if p53 is mutated (often the case in cancer) a clock regulated gene, p73, becomes a second-order effector for DNA damage during intrinsic apoptosis. It is also mentioned that considerable evidence exists showing DNA damage can also have effects on the clock by resetting its phase. Although, activation of the many intracellular signaling pathways can cause phase shifting to adjust the clock.
The article first discusses circadian clock regulation of DNA repair. It has only recently been discovered that the circadian clock is important in regulation of DNA …show more content…
Particularly, the clock has been tied to DNA damage repair checkpoint pathways. The ATR-Chk1 and ATM-Chk2 DNA damage signaling systems have both been tied to the circadian clock. The authors explain in detail how one must be cautioned against relying on data from tissue culture experiments. An example is given of an experiment that found mutations in the clock genes CLOCK, BMAL1, CRYs, and PERs had no effect on DNA repair pathways that were tested. Although, other experimental results show that at the level of an organism DNA repair pathways are effected and therefore circadian-controlled. The control mechanism is lost or overridden by homeostatic mechanisms in the tissue cultures. …show more content…
Apoptosis can be activated by sufficient DNA damage in cells, but the author puts it into its own specific relation to the clock. The circadian clock has recently been connected to both intrinsic and extrinsic apoptosis. The gene p53 is generally the dominant effector in promoting apoptosis in response to damaged DNA. However, if p53 is mutated (often the case in cancer) a clock regulated gene, p73, becomes a second-order effector for DNA damage during intrinsic apoptosis. It is also mentioned that considerable evidence exists showing DNA damage can also have effects on the clock by resetting its phase. Although, activation of the many intracellular signaling pathways can cause phase shifting to adjust the clock.