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NSF PR 96-11 - March 21, 1996
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"Light Sets the Molecular Controls of Circadian Rhythm"
Light sets the circadian rhythm by eliminating a key
protein needed for the molecular mechanism of the
body's clock, according to National Science Foundation
(NSF) scientists publishing in the March 22 issue
of the journal Science. The findings, from fruit fly
studies, may help explain light's effect on the daily
cycle that influences sleep, mental alertness, pain
sensitivity and temperature and hormone levels.
"Plants and animals, including insects, adjust their
intrinsic circadian cycles, which can range from about
23 to 25 hours, to the 24-hour solar day. We have
identified a molecular key to light's control in flies
and expect to find a similar mechanism in humans,
which may explain how people adjust their body clocks
after traveling across time zones," says Michael W.
Young, of Rockefeller University in New York, and
director of the NSF Science and Technology Center
for Biological Timing at Rockefeller.
Both fruit flies and humans have activity rhythms
that adapt perfectly to a 24-hour cycle of night and
day, or can be set to new time zones by light. The
influence of light is quite strong, Young notes. For
example, fruit flies raised in total darkness maintain
an activity rhythm of about 23.5 hours, but a brief
period in light can either delay or advance the cycle,
depending on the timing of the light exposure within
the cycle.
In the fly, the rhythm is set by the action of two
proteins, PER and TIM, made by the period (per) and
timeless (tim) genes, respectively. All cells of the
fly have per and tim genes, but the brain cells set
the body clock. PER and TIM proteins accumulate in
the nuclei of eye cells sensitive to light, called
photoreceptors, as well as pacemaker cells of the
central brain.
The fly circadian cycle begins around noon when the
per and tim genes transcribe their DNA into RNA, molecules
essential to create the PER and TIM proteins, but
only after sunset does the accumulated RNA prompt
the cell to stockpile the PER and TIM proteins. At
night, the proteins pair and migrate into the nucleus,
home to cells' genetic material. About four hours
before dawn, the level of PER/TIM protein complexes
peaks, which signals the per and tim genes to stop
making RNA and, hence, the protein complexes. Near
dawn, the PER/TIM protein complexes disintegrate.
With the complexes depleted, the per and tim genes
begin to make RNA again by midday. The scientists
found that the TIM and PER proteins need each other
to get into the nucleus. However, if flies are exposed
to light, one of the proteins, TIM, rapidly degrades,
which blocks the movement of the remaining protein
to the nucleus.
"In the natural environment, even though RNA levels
have been rising since midday, sunlight keeps TIM
protein from accumulating until nightfall," explains
Young. "This postponement delays the binding and nuclear
activity of the PER and TIM proteins until the night
part of the cycle."
The findings also suggest how light exposure at the
different times of day adapts the rhythm, such as
adjusting to a new time zone. For example, Young and
his colleagues found that flies exposed to one hour
of daylight in the evening, around 10 p.m., delayed
the normal night time accumulation of the TIM protein,
and postponed the behavioral cycle by four to five
hours, as if the fly were adapting to westward travel.
TIM proteins did accumulate later, in keeping with
the observed behavioral delay, Young notes. In contrast,
flies exposed to daylight an hour before dawn prematurely
lost their TIM proteins, which did not reappear until
the following afternoon. This light exposure advanced
the behavioral rhythm of the flies by one to two hours,
an adaptation expected for flies traveling east.
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