Author Archives: Bora Zivkovic

Interesting, if you are in the field:
The Neurospora Checkpoint Kinase 2: A Regulatory Link Between the Circadian and Cell Cycles
by António M. Pregueiro, Qiuyun Liu, Christopher L. Baker, Jay C. Dunlap, Jennifer J. Loros

The clock gene period-4 (prd-4) in Neurospora was identified by a single allele displaying shortened circadian period and altered temperature compensation. Positional cloning followed by functional tests show that PRD-4 is an ortholog of mammalian checkpoint kinase 2 (Chk2). Expression of prd-4 is regulated by the circadian clock and, reciprocally, PRD-4 physically interacts with the clock component FRQ, promoting its phosphorylation. DNA-damaging agents can reset the clock in a manner that depends on time of day, and this resetting is dependent on PRD-4. Thus, prd-4, the Neurospora Chk2, identifies a molecular link that feeds back conditionally from circadian output to input and the cell cycle.

It has been known for decades that scheduled meals can entrain the circadian clock. In some species (e.g., in some birds), regular timing of feeding entrains the main circadian system of the body in the suprachiasmatic (SCN) area of the hypothalamus, the retina and the pineal. In other species (e.g., rodents), it appears that the food-entrainable oscillator is anatomically and functionally distinct from the main pacemaker in the SCN.
Researchers working on different species discovered different properties and different anatomical locations for the food-entrainable clock. Now, a study from UT Southwestern Medical Center takes yet another look at the location of the food clock in mice, using expression of Period, a canonical clock gene, as the marker for the clock activity:
Timing of Food Consumption Activates Genes in Specific Brain Area:

The researchers put the mice on a 12-hour light/dark cycle, and provided food for four hours in the middle of the light portion. Because mice normally feed at night, this pattern is similar to humans eating at inappropriate times. Dysfunctional eating patterns play a role in human obesity, particularly in the nocturnal eating often seen in obese people, the researchers note.
The mice soon fell into a pattern of searching for food two hours before each feeding time. They also flipped their normal day/night behavior, ignoring the natural cue that day is their usual time to sleep. After several days, the researchers found that the daily activation cycle of Per genes in the SCN was not affected by the abnormal feeding pattern.
However, in a few different areas of the brain, particularly a center called the dorsomedial hypothamalic nucleus or DMH, the Per genes turned on strongly in sync with feeding time after seven days. When the mice subsequently went two days without food, the genes continued to turn on in sync with the expected feeding time.

I wonder what would have happened if instead of fasting, they gave food ad libitum at the end of the experiment. Also, what would have happened if either the whole experiment or that last 2-day bit was performed in constant darkness?
The paper is coming out on August 8 in PNAS. If there is something in the paper that the press release did not get right, I’ll be sure to tell you at that time.