Oscillations in levels of both per transcript and its corresponding protein PER have a period of approximately 24 hours and together play a central role in the molecular mechanism of the Drosophila biological clock driving circadian rhythms in eclosion and locomotor activity.
[1] The period gene and three mutants (perS, perL, and per0) were isolated in an EMS mutagenesis screen by Ronald Konopka and Seymour Benzer in 1971.
[5] In Drosophila, per mRNA levels oscillate with a period of approximately 24 hours, peaking during the early subjective night.
[7] This CLOCK/CYCLE complex acts as a transcriptional activator for per and tim by binding to specific enhancers (called E-boxes) of their promoters.
[11] This PER/CRY complex moves into the nucleus upon phosphorylation by CK1-epsilon (casein kinase 1 epsilon) and inhibits the CLK/BMAL1 heterodimer, the transcription factor that is bound to the E-boxes of the three per and two cry promoters by basic helix-loop-helix (BHLH) DNA-binding domains.
[12] Two years later, Albrecht et al. found genetic evidence to support this result when they discovered that mPer1 mutants are not able to advance the clock in response to a late-night light pulse (ZT22) and that mPer2 mutants are not able to delay the clock in response to an early night light pulse (ZT14).
[17] This is thought to be caused by mPer2 circadian deregulation of common tumor suppression and cell cycle regulation genes, such as Cyclin D1, Cyclin A, Mdm-2, and Gadd45α, as well as the transcription factor c-myc, which is directly controlled by circadian regulators through E box-mediated reactions.
[7] CRY has two human homologs, CRY1 and CRY2, which was discovered by Edmund A. Griffin, Jr., David Staknis and Charles J. Weitz to encompass light-independent interactions with CLOCK and BMAL1.
People suffering from the disorder have a shorter period and advanced phase where they go to sleep in the early evening (around 7pm) and wake up before sunrise (around 4am).
[25] Chronotherapy is sometimes used as a treatment, as an attempt to alter the phase of the individual's clock using cycles of bright light.