Phosphorylation of the Cryptochrome 1 C-terminal Tail Regulates Circadian Period Length

Loss or inhibition of DNA-dependent protein kinase results in circadian rhythms with abnormally long periods.

• The CRY proteins are essential for regulating the activity of key components in the mammalian circadian clock.
• A specific interaction was identified between CRY proteins and the catalytic subunit of DNA-dependent protein kinase.
• Phosphomimetic mutation at serine 588 in mouse CRY1 leads to long period rhythms, similar to the effects of inhibiting DNA-PK.
• Phosphorylation at serine 588 increases CRY1 protein stability and prevents its degradation by FBXL3.
• Phosphorylation of CRY1 at this site follows a rhythmic pattern in mouse liver nuclei, peaking during the circadian day when CRY1 levels drop.

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