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Description:
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Circadian rhythms are visible as daily oscillations in biochemical ,
physiological , or behavioral processes . These rhythms are produced by an
endogenous clock that maintains synchrony with the external environment
through responses to external stimuli such as light or temperature . The clock , in
turn , coordinates internal processes in a time -dependent fashion . Genetic and
molecular analysis of the filamentous fungus Neurospora crassa has
demonstrated that the products of the frequency (frq ) and white -collar (wc -1 and
wc -2 ) genes interact to form an interlocked feedback loop that lies at the heart of
the clock in this fungus . This feedback loop , termed the FRQ /WC oscillator ,
produces a ~24h oscillation in frq mRNA , FRQ protein , and WC -1 protein . In
turn , the FRQ /WC oscillator regulates rhythmic behavior and gene expression .
The goal of this dissertation is to understand how rhythmic outputs are regulated
by the FRQ /WC oscillator in Neurospora .
To this end , we have taken a microarray approach to first determine the
extent of clock -controlled gene expression in Neurospora . Here , we show that
circadian regulation of gene expression is widespread ; 145 genes , representing
20 % of the genes we analyzed , are clock -controlled . We show that clockregulation
is complex ; clock -controlled genes peak at all phases of the circadian
cycle . Furthermore , we demonstrate the clock regulates diverse biological
processes , such as intermediary metabolism , translation , sexual development
and asexual development . WC -1 is required for all light - and clock -regulated
gene expression in Neurospora . We have shown that overexpression of WC -1
is sufficient to activate clock -controlled gene expression , but is not sufficient to
induce all light -regulated genes in Neurospora . This result indicates that cycling
of WC -1 is sufficient to regulate rhythmic expression of a subset of clockcontrolled
genes . Conversely , a post -translational mechanism underlies WC -1
mediated light signal transduction in Neurospora . Finally , we have
demonstrated the Neurospora circadian system is comprised of mutually
coupled oscillators that interact to regulate output gene expression in the fungus . |