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post-transcriptional modifications
Timeless
Period
Timeless
Period
Timeless
Cryptochrome
Clock
Cycle
Timeless
period, timeless
E-box
Timeless
degradation
Figure 1.2 The core clock in Drosophila. (A) The transcription factors CYCLE and CLOCK transcriptionally activate period and timeless. The
period and timeless mRNAs are transported to the cytoplasm in the early evening where they are translated into their respective proteins.
Once PERIOD and TIMELESS proteins are modified by phosphatases and kinases, they are translocated as a dimer to the nucleus in the late
evening. Once in the nucleus, PERIOD - TIMELESS dimers inhibit the transcriptional activity of CLOCK - CYCLE, resulting in a decline in period
and timeless mRNA levels. Nuclear TIMELESS and PERIOD are then degraded, allowing the derepression of period and timeless promoters,
which starts the cycle all over again. (B) In the presence of light, the protein CRYPTOCHROME binds TIMELESS, preventing its dimerization
with PERIOD and leading to its degradation. This cycle continues in constant darkness but is amplified in light
dark cycles, when the blue light
-
receptor CRYPTOCHROME is activated. When the PERIOD
TIMELESS heterodimer is accumulating in the early evening, light retards the accu-
-
mulation of the PERIOD
TIMELESS dimer and sets the clock back. When PERIOD
TIMELESS are degrading late in the night, light accelerates
-
-
this breakdown and sets the clock ahead.
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