The molecular workings of the Neurospora biological clock

Novartis Found Symp. 2003:253:184-98; discussion 102-9, 198-202, 281-4.


In Neurosporacrassa the FRQ/WC feedback loop has been shown to be central to the function of the circadian clock. Similar to other eukaryotic systems it is based on a transcription-translation PAS heterodimer type feedback. FRQ levels cycle with a period identical to that of the Neurospora circadian cycle and its expression is rapidly induced by light. A complex of White Collar 1 (WC-1) and White Collar 2 (WC-2) (the WCC) is required for the transcriptional activation of frq. The oscillation in frq message is transcriptionally regulated via a single necessary and sufficient cis-acting element in the frq promoter, the Clock-Box (CB) bound by WCC. Light-induction of frq transcription is mediated by WCC binding to two cis-acting elements (LREs) in the frq promoter. WC-1, with flavin adenine dinucleotide (FAD) as a cofactor, is the blue-light photoreceptor. The original description of a frq-null strain, frq9, (Loros et al 1986) included a description of oscillations in asexual conidial banding that occasionally appeared following 3 to 7 days of arrhythmic development now referred to as FLO for FRQ-less oscillator. Unlike the intact clock, FLO period is sensitive to media composition. We have identified a circadianly regulated gene whose mutation interferes with FLO even under temperature entrainment conditions. This same mutation affects the circadian clock in a frq+ background causing a shorter period length as well as temperature response defects. This gene may be an entry point to study the connection between the biological clock and other basic cellular mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Circadian Rhythm / genetics*
  • Circadian Rhythm / physiology*
  • Circadian Rhythm / radiation effects
  • Fungal Proteins / genetics
  • Fungal Proteins / physiology
  • Genes, Fungal
  • Light
  • Models, Biological
  • Neurospora crassa / genetics*
  • Neurospora crassa / physiology*
  • Neurospora crassa / radiation effects
  • Photoreceptors, Microbial / genetics
  • Photoreceptors, Microbial / physiology
  • Photoreceptors, Microbial / radiation effects
  • Temperature


  • Fungal Proteins
  • Photoreceptors, Microbial