Gene Symbol: Cry1
Description: cryptochrome 1 (photolyase-like)
Alias: AU020726, AU021000, Phll1, cryptochrome-1
Species: mouse
Products:     Cry1

Top Publications

  1. Mrosovsky N. Further characterization of the phenotype of mCry1/mCry2-deficient mice. Chronobiol Int. 2001;18:613-25 pubmed
    ..One possible explanation of such predark activity is that some damped endogenous process is spared in mCry1/mCry2 double-knockout mice. ..
  2. Kondratov R, Kondratova A, Lee C, Gorbacheva V, Chernov M, Antoch M. Post-translational regulation of circadian transcriptional CLOCK(NPAS2)/BMAL1 complex by CRYPTOCHROMES. Cell Cycle. 2006;5:890-5 pubmed
    ..The products of these genes, CRY1 and CRY2, in turn repress CLOCK/BMAL1 transcriptional activity by an unknown mechanism...
  3. Gauger M, Sancar A. Cryptochrome, circadian cycle, cell cycle checkpoints, and cancer. Cancer Res. 2005;65:6828-34 pubmed
    ..b>Cryptochrome 1 and cryptochrome 2 proteins are core components of the mammalian circadian clock and mice mutated in both ..
  4. Lee S, Donehower L, Herron A, Moore D, Fu L. Disrupting circadian homeostasis of sympathetic signaling promotes tumor development in mice. PLoS ONE. 2010;5:e10995 pubmed publisher
    ..However, it remains unclear how circadian rhythm in cell proliferation is generated in vivo and why disruption of circadian rhythm may lead to tumorigenesis...
  5. Baggs J, Price T, DiTacchio L, Panda S, Fitzgerald G, Hogenesch J. Network features of the mammalian circadian clock. PLoS Biol. 2009;7:e52 pubmed publisher
    ..We propose that these network features act in concert as a genetic buffering system to maintain clock function in the face of genetic and environmental perturbation. ..
  6. Doi M, Takahashi Y, Komatsu R, Yamazaki F, Yamada H, Haraguchi S, et al. Salt-sensitive hypertension in circadian clock-deficient Cry-null mice involves dysregulated adrenal Hsd3b6. Nat Med. 2010;16:67-74 pubmed publisher
    ..We show that mice lacking the core clock components Cryptochrome-1 (Cry1) and Cryptochrome-2 (Cry2) (Cry-null mice) show salt-sensitive hypertension due to abnormally high synthesis of the ..
  7. Kang T, Reardon J, Sancar A. Regulation of nucleotide excision repair activity by transcriptional and post-transcriptional control of the XPA protein. Nucleic Acids Res. 2011;39:3176-87 pubmed publisher
    ..Collectively, the data reveal that XPA is a limiting factor in excision repair and that its level is coordinately regulated by the circadian clock, the ubiquitin-proteasome system and DNA damage. ..
  8. Miyamoto Y, Sancar A. Vitamin B2-based blue-light photoreceptors in the retinohypothalamic tract as the photoactive pigments for setting the circadian clock in mammals. Proc Natl Acad Sci U S A. 1998;95:6097-102 pubmed
    ..We have found that the two blue-light photoreceptors, cryptochromes 1 and 2 (CRY1 and CRY2), recently discovered in mammals are specifically expressed in the ganglion cell and inner nuclear layers ..
  9. Cheng M, Bullock C, Li C, Lee A, Bermak J, Belluzzi J, et al. Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus. Nature. 2002;417:405-10 pubmed
    ..The high expression of PKR2 mRNA within the SCN and the positive feedback of PK2 on its own transcription through activation of PKR2 suggest that PK2 may also function locally within the SCN to synchronize output. ..

More Information


  1. Asher G, Reinke H, Altmeyer M, Gutierrez Arcelus M, Hottiger M, Schibler U. Poly(ADP-ribose) polymerase 1 participates in the phase entrainment of circadian clocks to feeding. Cell. 2010;142:943-53 pubmed publisher
    ..Our results show that Parp-1 knockout mice exhibit impaired food entrainment of peripheral circadian clocks and support a role for PARP-1 in connecting feeding with the mammalian timing system. ..
  2. Grimaldi B, Bellet M, Katada S, Astarita G, Hirayama J, Amin R, et al. PER2 controls lipid metabolism by direct regulation of PPAR?. Cell Metab. 2010;12:509-20 pubmed publisher
    ..Our findings support a scenario in which PER2 controls the proadipogenic activity of PPAR? by operating as its natural modulator, thereby revealing potential avenues of pharmacological and therapeutic intervention. ..
  3. Naruse Y, Oh hashi K, Iijima N, Naruse M, Yoshioka H, Tanaka M. Circadian and light-induced transcription of clock gene Per1 depends on histone acetylation and deacetylation. Mol Cell Biol. 2004;24:6278-87 pubmed
    ..Mouse CRY1 (mCRY1) repressed transcription with HDACs and mSin3B, which was relieved by the HDAC inhibitor trichostatin A (TSA)..
  4. Kang T, Reardon J, Kemp M, Sancar A. Circadian oscillation of nucleotide excision repair in mammalian brain. Proc Natl Acad Sci U S A. 2009;106:2864-7 pubmed publisher
    ..The circadian oscillation of the repair capacity is caused at least in part by the circadian oscillation of the xeroderma pigmentosum A DNA damage recognition protein. ..
  5. Lee C, Weaver D, Reppert S. Direct association between mouse PERIOD and CKIepsilon is critical for a functioning circadian clock. Mol Cell Biol. 2004;24:584-94 pubmed
    ..We thus propose that the CKIepsilon-binding domain is critical not only for mPER phosphorylation but also for a functioning circadian clock. ..
  6. Van Gelder R, Wee R, Lee J, Tu D. Reduced pupillary light responses in mice lacking cryptochromes. Science. 2003;299:222 pubmed
  7. Yagita K, Yamaguchi S, Tamanini F, van der Horst G, Hoeijmakers J, Yasui A, et al. Dimerization and nuclear entry of mPER proteins in mammalian cells. Genes Dev. 2000;14:1353-63 pubmed
    ..Deletion analysis suggests that the interplay of the CLD and NLS proposed to regulate nuclear entry of PER in Drosophila is conserved in mammals, but with the novel twist that mPER3 can act as the dimerizing partner. ..
  8. Siepka S, Yoo S, Park J, Song W, Kumar V, Hu Y, et al. Circadian mutant Overtime reveals F-box protein FBXL3 regulation of cryptochrome and period gene expression. Cell. 2007;129:1011-23 pubmed
    ..In Ovtm mice, expression of the PERIOD proteins PER1 and PER2 is reduced; however, the CRY proteins CRY1 and CRY2 are unchanged...
  9. Kiyohara Y, Tagao S, Tamanini F, Morita A, Sugisawa Y, Yasuda M, et al. The BMAL1 C terminus regulates the circadian transcription feedback loop. Proc Natl Acad Sci U S A. 2006;103:10074-9 pubmed
    ..for transcriptional activation, as well as for association with the circadian transcriptional repressor CRYPTOCHROME 1 (CRY1), depending on the coexistence of CLOCK protein...
  10. Lamia K, Sachdeva U, DiTacchio L, Williams E, Alvarez J, Egan D, et al. AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science. 2009;326:437-40 pubmed publisher
    ..adenosine monophosphate-activated protein kinase (AMPK) phosphorylates and destabilizes the clock component cryptochrome 1 (CRY1)...
  11. Ono D, Honma S, Honma K. Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus. Nat Commun. 2013;4:1666 pubmed publisher
    ..Nevertheless, cultured suprachiasmatic nucleus (SCN) of neonatal Cry double deficient (Cry1(-/-)/Cry2(-/-)) mice exhibit circadian rhythms that damp out in several cycles...
  12. Oster H, Yasui A, van der Horst G, Albrecht U. Disruption of mCry2 restores circadian rhythmicity in mPer2 mutant mice. Genes Dev. 2002;16:2633-8 pubmed
    ..Among the components driving the mammalian circadian clock are the Period 1 and 2 (mPer1 and mPer2) and Cryptochrome 1 and 2 (mCry1 and mCry2) genes...
  13. Engelen E, Janssens R, Yagita K, Smits V, van der Horst G, Tamanini F. Mammalian TIMELESS is involved in period determination and DNA damage-dependent phase advancing of the circadian clock. PLoS ONE. 2013;8:e56623 pubmed publisher
    ..Furthermore, we reveal that the N-terminus of TIM is sufficient for interaction with CRY1 and CHK1 as well for homodimerization, and the C-terminus is necessary for nuclear localization...
  14. Scoma H, Humby M, Yadav G, Zhang Q, Fogerty J, Besharse J. The de-ubiquitinylating enzyme, USP2, is associated with the circadian clockwork and regulates its sensitivity to light. PLoS ONE. 2011;6:e25382 pubmed publisher
    ..Rhythmic expression of USP2 in the SCN and other tissues offers a new level of control of the clock machinery through de-ubiqutinylation and suggests a role for USP2 during circadian adaptation to environmental day length changes. ..
  15. Maywood E, Chesham J, O Brien J, Hastings M. A diversity of paracrine signals sustains molecular circadian cycling in suprachiasmatic nucleus circuits. Proc Natl Acad Sci U S A. 2011;108:14306-11 pubmed publisher
    ..Thus, a hierarchy of paracrine neuropeptidergic signals determines cell- and circuit-level circadian pacemaking in the SCN. ..
  16. Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C, Kreppel F, et al. SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell. 2008;134:317-28 pubmed publisher
    ..for high-magnitude circadian transcription of several core clock genes, including Bmal1, Rorgamma, Per2, and Cry1. SIRT1 binds CLOCK-BMAL1 in a circadian manner and promotes the deacetylation and degradation of PER2...
  17. Kojima S, Matsumoto K, Hirose M, Shimada M, Nagano M, Shigeyoshi Y, et al. LARK activates posttranscriptional expression of an essential mammalian clock protein, PERIOD1. Proc Natl Acad Sci U S A. 2007;104:1859-64 pubmed
    ..These data indicate that mLARKs are novel posttranscriptional regulators of mammalian circadian clocks. ..
  18. Liu A, Welsh D, Ko C, Tran H, Zhang E, Priest A, et al. Intercellular coupling confers robustness against mutations in the SCN circadian clock network. Cell. 2007;129:605-16 pubmed
    ..We discovered that Per1 and Cry1 are required for sustained rhythms in peripheral tissues and cells, and in neurons dissociated from the ..
  19. Ye R, Selby C, Ozturk N, Annayev Y, Sancar A. Biochemical analysis of the canonical model for the mammalian circadian clock. J Biol Chem. 2011;286:25891-902 pubmed publisher
    ..These findings support some aspects of the canonical model, but also suggest that some key features of the model need to be revised. ..
  20. Oishi K, Miyazaki K, Kadota K, Kikuno R, Nagase T, Atsumi G, et al. Genome-wide expression analysis of mouse liver reveals CLOCK-regulated circadian output genes. J Biol Chem. 2003;278:41519-27 pubmed
    ..We also compared expression profiles with those of Cryptochromes (Cry1 and Cry2) double knockout mice...
  21. Mendoza J, Albrecht U, Challet E. Behavioural food anticipation in clock genes deficient mice: confirming old phenotypes, describing new phenotypes. Genes Brain Behav. 2010;9:467-77 pubmed publisher
    ..Furthermore, we found that Per1(-/-);Per2(Brdm1) and Per2(Brdm1);Cry1(-/-) double mutant animals did not display a stable and significant FAA either in DD or LD...
  22. Maywood E, O Brien J, Hastings M. Expression of mCLOCK and other circadian clock-relevant proteins in the mouse suprachiasmatic nuclei. J Neuroendocrinol. 2003;15:329-34 pubmed
  23. Ozturk N, Lee J, Gaddameedhi S, Sancar A. Loss of cryptochrome reduces cancer risk in p53 mutant mice. Proc Natl Acad Sci U S A. 2009;106:2841-6 pubmed publisher
    ..These results suggest alternative therapeutic approaches in management of cancers associated with a p53 mutation. ..
  24. Chen R, Schirmer A, Lee Y, Lee H, Kumar V, Yoo S, et al. Rhythmic PER abundance defines a critical nodal point for negative feedback within the circadian clock mechanism. Mol Cell. 2009;36:417-30 pubmed publisher
    ..In this study, however, constitutive expression of PER, and not CRY1, severely disrupted the clock in fibroblasts and liver...
  25. Yagita K, Tamanini F, Yasuda M, Hoeijmakers J, van der Horst G, Okamura H. Nucleocytoplasmic shuttling and mCRY-dependent inhibition of ubiquitylation of the mPER2 clock protein. EMBO J. 2002;21:1301-14 pubmed
    ..On the basis of these data we propose a model in which shuttling mPER2 is ubiquitylated and degraded by the proteasome unless it is retained in the nucleus by mCRY proteins. ..
  26. Doi M, Ishida A, Miyake A, Sato M, Komatsu R, Yamazaki F, et al. Circadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus. Nat Commun. 2011;2:327 pubmed publisher
    ..Thus, RGS16-dependent temporal regulation of intracellular G protein signalling coordinates the intercellular synchrony of SCN pacemaker neurons and thereby defines the 24 h rhythm in behaviour. ..
  27. Chaves I, Yagita K, Barnhoorn S, Okamura H, van der Horst G, Tamanini F. Functional evolution of the photolyase/cryptochrome protein family: importance of the C terminus of mammalian CRY1 for circadian core oscillator performance. Mol Cell Biol. 2006;26:1743-53 pubmed
    ..While plant and fly CRYs act as circadian photoreceptors, using the C terminus for light signaling, mammalian CRY1 and CRY2 are integral components of the circadian oscillator...
  28. Duong H, Robles M, Knutti D, Weitz C. A molecular mechanism for circadian clock negative feedback. Science. 2011;332:1436-9 pubmed publisher
    ..These findings provide a function for the PER complex and a molecular mechanism for circadian clock negative feedback. ..
  29. Koike N, Yoo S, Huang H, Kumar V, Lee C, Kim T, et al. Transcriptional architecture and chromatin landscape of the core circadian clock in mammals. Science. 2012;338:349-54 pubmed publisher
    ..We also find that circadian modulation of RNAPII recruitment and chromatin remodeling occurs on a genome-wide scale far greater than that seen previously by gene expression profiling. ..
  30. Thresher R, Vitaterna M, Miyamoto Y, Kazantsev A, Hsu D, Petit C, et al. Role of mouse cryptochrome blue-light photoreceptor in circadian photoresponses. Science. 1998;282:1490-4 pubmed
    ..These data are consistent with the hypothesis that CRY2 protein modulates circadian responses in mice and suggest that cryptochromes have a role in circadian photoreception in mammals. ..
  31. Miyamoto Y, Sancar A. Circadian regulation of cryptochrome genes in the mouse. Brain Res Mol Brain Res. 1999;71:238-43 pubmed
    ..In humans and mice, two cryptochromes, called CRY1 and CRY2, have been identified...
  32. Yamaguchi S, Isejima H, Matsuo T, Okura R, Yagita K, Kobayashi M, et al. Synchronization of cellular clocks in the suprachiasmatic nucleus. Science. 2003;302:1408-12 pubmed
    ..Na+-dependent action potentials contributed to establishing cellular synchrony and maintaining spontaneous oscillation across the SCN. ..
  33. Cretenet G, Le Clech M, Gachon F. Circadian clock-coordinated 12 Hr period rhythmic activation of the IRE1alpha pathway controls lipid metabolism in mouse liver. Cell Metab. 2010;11:47-57 pubmed publisher
    ..The resulting aberrant circadian lipid metabolism in mice devoid of the circadian clock could be involved in the appearance of the associated metabolic syndrome. ..
  34. Vitaterna M, Selby C, Todo T, Niwa H, Thompson C, Fruechte E, et al. Differential regulation of mammalian period genes and circadian rhythmicity by cryptochromes 1 and 2. Proc Natl Acad Sci U S A. 1999;96:12114-9 pubmed
    ..In this study, Cry1(-/-) and Cry1(-/-)Cry2(-/-) mice were generated and their circadian clocks were analyzed at behavioral and ..
  35. Sasaki M, Yoshitane H, Du N, Okano T, Fukada Y. Preferential inhibition of BMAL2-CLOCK activity by PER2 reemphasizes its negative role and a positive role of BMAL2 in the circadian transcription. J Biol Chem. 2009;284:25149-59 pubmed publisher
    ..Collectively, it is strongly suggested that BMAL2 plays an active role in the circadian transcription. ..
  36. Ramsey K, Yoshino J, Brace C, Abrassart D, Kobayashi Y, Marcheva B, et al. Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science. 2009;324:651-4 pubmed publisher
    ..In turn, the circadian transcription factor CLOCK binds to and up-regulates Nampt, thus completing a feedback loop involving NAMPT/NAD+ and SIRT1/CLOCK:BMAL1. ..
  37. Preitner N, Damiola F, Lopez Molina L, Zakany J, Duboule D, Albrecht U, et al. The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell. 2002;110:251-60 pubmed
    ..While REV-ERBalpha influences the period length and affects the phase-shifting properties of the clock, it is not required for circadian rhythm generation. ..
  38. Fu L, Patel M, Bradley A, Wagner E, Karsenty G. The molecular clock mediates leptin-regulated bone formation. Cell. 2005;122:803-15 pubmed
    ..Thus, leptin determines the extent of bone formation by modulating, via sympathetic signaling, osteoblast proliferation through two antagonistic pathways, one of which involves the molecular clock. ..
  39. Gotter A. Tipin, a novel timeless-interacting protein, is developmentally co-expressed with timeless and disrupts its self-association. J Mol Biol. 2003;331:167-76 pubmed
    ..Together, these results indicate that mTIM forms a functional complex with TIPIN, and provide a starting point from which to link mTim to biochemical pathways controlling vital cellular functions. ..
  40. Etchegaray J, Yang X, Debruyne J, Peters A, Weaver D, Jenuwein T, et al. The polycomb group protein EZH2 is required for mammalian circadian clock function. J Biol Chem. 2006;281:21209-15 pubmed
    ..These results indicate that EZH2 is important for the maintenance of circadian rhythms and extend the activity of the polycomb group proteins to the core clockwork mechanism of mammals. ..
  41. Zhao W, Malinin N, Yang F, Staknis D, Gekakis N, Maier B, et al. CIPC is a mammalian circadian clock protein without invertebrate homologues. Nat Cell Biol. 2007;9:268-75 pubmed
    ..Our results suggest that negative feedback in the mammalian circadian clock is divided into distinct pathways, and that the addition of new genes has contributed to the complexity of vertebrate clocks. ..
  42. Maywood E, Drynan L, Chesham J, Edwards M, Dardente H, Fustin J, et al. Analysis of core circadian feedback loop in suprachiasmatic nucleus of mCry1-luc transgenic reporter mouse. Proc Natl Acad Sci U S A. 2013;110:9547-52 pubmed publisher
    ..We therefore created a mouse, B6.Cg-Tg(Cry1-luc)01Ld, carrying a transgene (mCry1-luc) consisting of mCry1 elements containing an E-box and E'-box driving ..
  43. Zhang E, Liu Y, Dentin R, Pongsawakul P, Liu A, Hirota T, et al. Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis. Nat Med. 2010;16:1152-6 pubmed publisher
    ..of gene expression is achieved by two transcriptional activators, Clock and Bmal1, which stimulate cryptochrome (Cry1 and Cry2) and Period (Per1, Per2 and Per3) repressors that feed back on Clock-Bmal1 activity...
  44. Busino L, Bassermann F, Maiolica A, Lee C, Nolan P, Godinho S, et al. SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins. Science. 2007;316:900-4 pubmed
    ..Among its downstream targets, two genes, Cry1 and Cry2, encode inhibitors of the Clock-Bmal1 complex that establish a negative-feedback loop...
  45. Kobayashi K, Kanno S, Smit B, van der Horst G, Takao M, Yasui A. Characterization of photolyase/blue-light receptor homologs in mouse and human cells. Nucleic Acids Res. 1998;26:5086-92 pubmed
    ..C-terminal region of the mouse CRY2 protein contains a unique nuclear localization signal, which is absent in the CRY1 protein. The N-terminal region of CRY1 was shown to contain the mitochondrial transport signal...
  46. Kume K, Zylka M, Sriram S, Shearman L, Weaver D, Jin X, et al. mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell. 1999;98:193-205 pubmed
    ..Luciferase reporter gene assays show that mCRY1 or mCRY2 alone abrogates CLOCK:BMAL1-E box-mediated transcription. The mPER and mCRY proteins appear to inhibit the transcriptional complex differentially. ..
  47. Okamura H, Miyake S, Sumi Y, Yamaguchi S, Yasui A, Muijtjens M, et al. Photic induction of mPer1 and mPer2 in cry-deficient mice lacking a biological clock. Science. 1999;286:2531-4 pubmed
    ..Thus, mCRY1 and mCRY2 are dispensable for light-induced phase shifting of the biological clock. ..
  48. Vollmers C, Gill S, DiTacchio L, Pulivarthy S, Le H, Panda S. Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression. Proc Natl Acad Sci U S A. 2009;106:21453-8 pubmed publisher
    ..Our findings show that both temporal pattern of food intake and the circadian clock drive rhythmic transcription, thereby highlighting temporal regulation of hepatic transcription as an emergent property of the circadian system. ..
  49. Langmesser S, Tallone T, Bordon A, Rusconi S, Albrecht U. Interaction of circadian clock proteins PER2 and CRY with BMAL1 and CLOCK. BMC Mol Biol. 2008;9:41 pubmed publisher
    ..mechanism how positive and negative components of the clock interplay, we characterized the interactions of PER2, CRY1 and CRY2 with BMAL1 and CLOCK using a mammalian two-hybrid system and co-immunoprecipitation assays...
  50. Albus H, Bonnefont X, Chaves I, Yasui A, Doczy J, van der Horst G, et al. Cryptochrome-deficient mice lack circadian electrical activity in the suprachiasmatic nuclei. Curr Biol. 2002;12:1130-3 pubmed
    ..The Cryptochrome 1 and 2 genes are indispensable for molecular core oscillator function, as evident from the arrhythmic wheel-..
  51. Woo K, Ha D, Lee K, Kim D, Kim T, Kim K. Circadian amplitude of cryptochrome 1 is modulated by mRNA stability regulation via cytoplasmic hnRNP D oscillation. Mol Cell Biol. 2010;30:197-205 pubmed publisher
    ..In the present study, we investigated the role of the 3'-untranslated region (3'UTR) of the mouse cryptochrome 1 (mcry1) gene at the posttranscriptional level...
  52. Selby C, Thompson C, Schmitz T, Van Gelder R, Sancar A. Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in mice. Proc Natl Acad Sci U S A. 2000;97:14697-702 pubmed
  53. Hashiramoto A, Yamane T, Tsumiyama K, Yoshida K, Komai K, Yamada H, et al. Mammalian clock gene Cryptochrome regulates arthritis via proinflammatory cytokine TNF-alpha. J Immunol. 2010;184:1560-5 pubmed publisher
    ..Deletion of Cry1 and Cry2 results in an increase in the number of activated CD3(+) CD69(+) T cells and a higher production of TNF-..
  54. Czarna A, Berndt A, Singh H, Grudziecki A, Ladurner A, Timinszky G, et al. Structures of Drosophila cryptochrome and mouse cryptochrome1 provide insight into circadian function. Cell. 2013;153:1394-405 pubmed publisher
    Drosophila cryptochrome (dCRY) is a FAD-dependent circadian photoreceptor, whereas mammalian cryptochromes (CRY1/2) are integral clock components that repress mCLOCK/mBMAL1-dependent transcription...
  55. Oster H, Baeriswyl S, van der Horst G, Albrecht U. Loss of circadian rhythmicity in aging mPer1-/-mCry2-/- mutant mice. Genes Dev. 2003;17:1366-79 pubmed
  56. Sujino M, Masumoto K, Yamaguchi S, van der Horst G, Okamura H, Inouye S. Suprachiasmatic nucleus grafts restore circadian behavioral rhythms of genetically arrhythmic mice. Curr Biol. 2003;13:664-8 pubmed
  57. Hirayama J, Sahar S, Grimaldi B, Tamaru T, Takamatsu K, Nakahata Y, et al. CLOCK-mediated acetylation of BMAL1 controls circadian function. Nature. 2007;450:1086-90 pubmed
    ..BMAL1 acetylation facilitates recruitment of CRY1 to CLOCK-BMAL1, thereby promoting transcriptional repression...
  58. van der Horst G, Muijtjens M, Kobayashi K, Takano R, Kanno S, Takao M, et al. Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms. Nature. 1999;398:627-30 pubmed
    ..This suggests that, in addition to a possible photoreceptor and antagonistic clock-adjusting function, both proteins are essential for the maintenance of circadian rhythmicity. ..
  59. Schmalen I, Reischl S, Wallach T, Klemz R, Grudziecki A, Prabu J, et al. Interaction of circadian clock proteins CRY1 and PER2 is modulated by zinc binding and disulfide bond formation. Cell. 2014;157:1203-15 pubmed publisher
    ..clock, we have determined the crystal structure of a complex comprising the photolyase homology region of mouse CRY1 (mCRY1) and a C-terminal mouse PER2 (mPER2) fragment...
  60. Czarna A, Breitkreuz H, Mahrenholz C, Arens J, Strauss H, Wolf E. Quantitative analyses of cryptochrome-mBMAL1 interactions: mechanistic insights into the transcriptional regulation of the mammalian circadian clock. J Biol Chem. 2011;286:22414-25 pubmed publisher
    ..Moreover, our study suggests the design of peptidic inhibitors targeting the interaction of the mCRY1 tail with mBMAL1. ..
  61. Amano T, Matsushita A, Hatanaka Y, Watanabe T, Oishi K, Ishida N, et al. Expression and functional analyses of circadian genes in mouse oocytes and preimplantation embryos: Cry1 is involved in the meiotic process independently of circadian clock regulation. Biol Reprod. 2009;80:473-83 pubmed publisher
    In mammals, circadian genes, Clock, Arntl (also known as Bmal1), Cry1, Cry2, Per1, Per2, and Per3, are rhythmically transcribed every 24 h in almost all organs and tissues to tick the circadian clock...
  62. Kang T, Lindsey Boltz L, Reardon J, Sancar A. Circadian control of XPA and excision repair of cisplatin-DNA damage by cryptochrome and HERC2 ubiquitin ligase. Proc Natl Acad Sci U S A. 2010;107:4890-5 pubmed publisher
    ..These findings may be used as a guide for timing of cisplatin chemotherapy. ..
  63. Xu Y, Toh K, Jones C, Shin J, Fu Y, Ptacek L. Modeling of a human circadian mutation yields insights into clock regulation by PER2. Cell. 2007;128:59-70 pubmed
    ..Altering CKIdelta dosage modulates the S662 phenotype demonstrating that CKIdelta can regulate period through PER2 in vivo. Modeling a naturally occurring human variant in mice has yielded novel insights into PER2 regulation. ..
  64. van der Spek P, Kobayashi K, Bootsma D, Takao M, Eker A, Yasui A. Cloning, tissue expression, and mapping of a human photolyase homolog with similarity to plant blue-light receptors. Genomics. 1996;37:177-82 pubmed
    ..In situ hybridization with a cDNA-derived probe localized this human gene to chromosome 12q23-q24.1. Southern analysis of the cloned human gene suggests a wide distribution of the gene family in various species. ..
  65. Bur I, Cohen Solal A, Carmignac D, Abecassis P, Chauvet N, Martin A, et al. The circadian clock components CRY1 and CRY2 are necessary to sustain sex dimorphism in mouse liver metabolism. J Biol Chem. 2009;284:9066-73 pubmed publisher
    ..Here we show that dimorphic liver metabolism is altered when the circadian regulators Cryptochromes, Cry1 and Cry2, are inactivated...
  66. Stratmann M, Stadler F, Tamanini F, van der Horst G, Ripperger J. Flexible phase adjustment of circadian albumin D site-binding protein (DBP) gene expression by CRYPTOCHROME1. Genes Dev. 2010;24:1317-28 pubmed publisher
    ..Here we describe a direct impact of CRYPTOCHROME1 (CRY1) on the phase of Dbp expression...
  67. Thompson C, Selby C, Partch C, Plante D, Thresher R, Araujo F, et al. Further evidence for the role of cryptochromes in retinohypothalamic photoreception/phototransduction. Brain Res Mol Brain Res. 2004;122:158-66 pubmed
  68. Iijima M, Yamaguchi S, van der Horst G, Bonnefont X, Okamura H, Shibata S. Altered food-anticipatory activity rhythm in Cryptochrome-deficient mice. Neurosci Res. 2005;52:166-73 pubmed
    ..However, it is also important to note that mCry deficiency affects the stability and development of RF-induced anticipatory locomotor activity. ..
  69. Koyanagi S, Hamdan A, Horiguchi M, Kusunose N, Okamoto A, Matsunaga N, et al. cAMP-response element (CRE)-mediated transcription by activating transcription factor-4 (ATF4) is essential for circadian expression of the Period2 gene. J Biol Chem. 2011;286:32416-23 pubmed publisher
    ..These results suggest that ATF4 is a component responsible for sustaining circadian oscillation of CRE-mediated gene expression and also constitute a molecular link connecting cAMP-dependent signaling to the circadian clock. ..
  70. Ukai Tadenuma M, Yamada R, Xu H, Ripperger J, Liu A, Ueda H. Delay in feedback repression by cryptochrome 1 is required for circadian clock function. Cell. 2011;144:268-81 pubmed publisher
    ..b>Cryptochrome 1 (Cry1), an essential clock component, displays evening-time expression and serves as a strong repressor at ..
  71. Schmutz I, Ripperger J, Baeriswyl Aebischer S, Albrecht U. The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors. Genes Dev. 2010;24:345-57 pubmed publisher
    ..The concept that PER2 may propagate clock information to metabolic pathways via nuclear receptors adds an important facet to the clock-dependent regulation of biological networks. ..
  72. Wisor J, O Hara B, Terao A, Selby C, Kilduff T, Sancar A, et al. A role for cryptochromes in sleep regulation. BMC Neurosci. 2002;3:20 pubmed
    The cryptochrome 1 and 2 genes (cry1 and cry2) are necessary for the generation of circadian rhythms, as mice lacking both of these genes (cry1,2-/-) lack circadian rhythms...