Cryptochrome circadian regulator 1 (CRY1)

Cryptochrome circadian regulator 1 (CRY1) is a transcriptional repressor and core component of the molecular circadian clock in mammals. It interacts with and inhibits the transcription factor CLOCK:BMAL1, thereby closing the negative feedback loop essential for circadian rhythm generation[2][5][6]. Beyond its canonical role in circadian timing, CRY1 regulates DNA repair by controlling homologous recombination factor expression, modulates cell proliferation, and is implicated in the progression of several cancers, especially prostate cancer, through androgen-regulated pathways and stabilization under genotoxic stress[1][3]. It also affects xenobiotic metabolism and acts independently from other clock proteins in various tissues. Variants in CRY1—such as CRY1Δ11—are established genetic causes of delayed sleep phase disorder due to altered repression of CLOCK:BMAL1 activity[5]. Experimental drugs like KL001 stabilize CRY1 and shed light on its druggability for circadian-related diseases and cancer[1][4]. Safety concerns mainly relate to dysregulated circadian function and DNA repair, which can promote tumorigenesis or sleep disorders if CRY1 is modulated inappropriately.

Other names

Cryptochrome-1PHLL1DSPDcryptochrome 1 (photolyase-like)cryptochrome circadian clock 1Cryptochrome circadian regulator 1CRY1

Stabilization of CRY1 leads to altered circadian period and increased DNA repair capacity (KL001)[1][4] Small molecules may modulate CRY1-dependent repression and feedback on circadian rhythm, influencing gene expression linked to proliferation and repair[4][1]