Functional Evolution of the Photolyase/Cryptochrome Protein Family: Importance of the C Terminus of Mammalian CRY1 for Circadian Core Oscillator Performance

The C-terminal extension of mammalian CRY1 is essential for its nuclear localization and function.

• The C-terminal extension contains a nuclear localization signal and a coiled-coil domain that facilitate nuclear localization through two independent mechanisms.
• This extension shifts the balance of mammalian CRY1/mammalian PER2 complexes towards the nucleus.
• Deletion of the entire C terminus prevents mammalian CRY1 from repressing CLOCK/BMAL1-mediated transcription.
• Fusion of a plant photolyase with the last 100 amino acids of mCRY1 enables it to gain the ability to repress transcription.
• The evolution of different C termini in cryptochromes has led to functional divergence from photolyase and within the cryptochrome family.

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