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Identification of interacting domain of mammalian cryptochrome with clock proteins, BMAL, Period, and CLOCK

Final Activity Report Summary - IOIDMC (Identification of interacting domain of mammalian cryptochrome with clock proteins, BMAL, Period, and CLOCK)

Circadian rhythms are the endogenous oscillations that occur with a periodicity of approximately 24 hours, and which regulate the biochemical and behavioural functions of organisms. Theses rhythms are achieved by the CLOCK proteins, which are located in the suprachiasmatic nuclei (SCN). The clockwork is made up of positive and negative transcriptional regulators. The CLOCK-BMAL1 heterodimer activates transcription of the period 2 (PER2) and CRY2 genes. The PER proteins interact with the CRY proteins; central sequences of the PER proteins interact with CKIe, and the resulting ternary complexes translocate into the nucleus, where they negatively regulate the transcription of PER and CRY genes. The PER and CRY proteins also positively regulate transcription of Bmal1.

In this study, the interacting domain of cryptochromes with BMAL and PER2 has been identified using a mammalian two-hybrid system. Our results indicated that in mice CRY2 carboxyl termini are responsible for the interactions with PER2. Further analysis has indicated one amino acid Arg is responsible for this interaction with PER2. Also, Analyses of Cryptochrome domain that participate interaction with BMAL1 revealed that both C- and N-termini participate such interaction. All these results can be utilised for the drug discovery against biological clock related diseases.