Froehlich Allan C, Pregueiro Antonio, Lee Kwangwon, Denault Deanna, Colot Hildur, Nowrousian Minou, Loros Jennifer J, Dunlap Jay C
Department of Genetics, Dartmouth Medical School, Hanover, NH 03755, USA.
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.
在粗糙脉孢菌中，FRQ/WC反馈环已被证明是生物钟功能的核心。与其他真核生物系统类似，它基于转录-翻译PAS异二聚体型反馈。FRQ水平的循环周期与粗糙脉孢菌的昼夜节律周期相同，并且其表达会被光迅速诱导。frq的转录激活需要白领1（WC-1）和白领2（WC-2）的复合物（WCC）。frq信使的振荡通过frq启动子中的单个必要且充分的顺式作用元件，即与WCC结合的生物钟框（CB）进行转录调控。frq转录的光诱导是由WCC与frq启动子中的两个顺式作用元件（LREs）结合介导的。WC-1以黄素腺嘌呤二核苷酸（FAD）作为辅因子，是蓝光光感受器。frq基因缺失菌株frq9的最初描述（Loros等人，1986年）包括对无性分生孢子带的振荡的描述，这种振荡偶尔会在3至7天的无节律发育后出现，现在称为FRQ缺失振荡器（FLO）。与完整的生物钟不同，FLO周期对培养基成分敏感。我们已经鉴定出一个受昼夜节律调控的基因，其突变即使在温度诱导条件下也会干扰FLO。相同的突变在frq+背景下影响生物钟，导致周期长度缩短以及温度响应缺陷。该基因可能是研究生物钟与其他基本细胞机制之间联系的切入点。
