A Mutant Drosophila Homolog of Mammalian Clock Disrupts
Cell, Vol. 93, 791±804, May 29, 1998, Copyright 1998 by Cell Press AMutantDrosophila Homolog of Mammalian Clock Disrupts Circadian Rhythms and Transcription of period and timeless Ravi Allada,*²³§ Neal E. White,³ Aronson et al., 1994; Shearman et al., 1997; Sun et al., W. Venus So,²³ Jeffrey C. Hall,²³ 1997; Tei et al., 1997). ²³ and Michael Rosbash* k In Drosophila, there are two well-characterized clock *Howard Hughes Medical Institute genes: period (per) and timeless (tim). Protein levels, ² NSF, Center for Biological Timing RNA levels, and transcription rates of these two genes ³ Department of Biology undergo robust circadian oscillations (Zerr et al., 1990; Brandeis University Hardin et al., 1990, 1992; Hardin, 1994; Sehgal et al., Waltham, Massachusetts 02254 1995; So and Rosbash, 1997). In addition, mutations § Department of Pathology in the two proteins (PER and TIM) alter or abolish the Brigham and Women's Hospital periodicity and phase of these rhythms, demonstrating Boston, Massachusetts 02115 that both proteins regulate their own transcription (Har- din et al., 1990; Sehgal et al., 1995; Marrus et al., 1996). Although there is no evidence indicating that the effects Summary on transcription are direct, PER contains a PAS domain, which has been shown to mediate interactions between We report the identification, characterization, and transcription factors (Huang et al., 1993; Lindebro et cloning of a novel Drosophila circadian rhythm gene, al., 1995). Most of these PAS-containing transcription dClock. The mutant, initially called Jrk, manifests dom- factors also contain the well-characterized basic helix- inant effects: heterozygous flies have a period alter- loop-helix (bHLH) DNA-binding domains (Crews, 1998).
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