Time at the end of the millennium: the Neurospora clock.

In the past two years we have entered the log phase for unraveling the molecular clockworks. Rapid progress in understanding the Neurospora clock has been complemented by a flood of information from diverse systems including cyanobacteria, insects and mice. There are broadly conserved features in transcription/translation based feedback loops. Conservation is also found at the sequence level, from fungi to mammals, in the PAS domains of the heterodimeric partners of the transcription factors that act as the positive components of the feedback cycle. Pivotal PAS proteins from Neurospora, the WCs, provide an evolutionary link connecting the clock in insects and mammals to the fungi and to light-harvesting proteins from bacteria.