Researcher: Kayıtmazbatır, Sibel Çal
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Kayıtmazbatır, Sibel Çal
Çal, Sibel
Çal, Sibel
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Publication Open Access CRY1-CBS binding regulates circadian clock function and metabolism(Wiley, 2021) Growe, Jacqueline; Selby, Christopher P.; Rhoades, Seth D.; Malik, Dania; Francey, Lauren J.; Sancar, Aziz; Kruger, Warren D.; Hogenesch, John B.; Weljie, Aalim; Anafi, Ron C.; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; N/A; Kayıtmazbatır, Sibel Çal; Öner, Haşimcan; Asımgil, Hande; Kavaklı, İbrahim Halil; PhD Student; Faculty Member; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; N/A; N/A; 40319Circadian disruption influences metabolic health. Metabolism modulates circadian function. However, the mechanisms coupling circadian rhythms and metabolism remain poorly understood. Here, we report that cystathionine beta-synthase (CBS), a central enzyme in one-carbon metabolism, functionally interacts with the core circadian protein cryptochrome 1 (CRY1). In cells, CBS augments CRY1-mediated repression of the CLOCK/BMAL1 complex and shortens circadian period. Notably, we find that mutant CBS-I278T protein, the most common cause of homocystinuria, does not bind CRY1 or regulate its repressor activity. Transgenic Cbs(Zn/Zn) mice, while maintaining circadian locomotor activity period, exhibit reduced circadian power and increased expression of E-BOX outputs. CBS function is reciprocally influenced by CRY1 binding. CRY1 modulates enzymatic activity of the CBS. Liver extracts from Cry1(-/-) mice show reduced CBS activity that normalizes after the addition of exogenous wild-type (WT) CRY1. Metabolomic analysis of WT, Cbs(Zn/Zn), Cry1(-/-), and Cry2(-/-) samples highlights the metabolic importance of endogenous CRY1. We observed temporal variation in one-carbon and transsulfuration pathways attributable to CRY1-induced CBS activation. CBS-CRY1 binding provides a post-translational switch to modulate cellular circadian physiology and metabolic control.