Regulation of Cell Cycle Progression by Circadian Rhythms in Cyanidioschyzon merolae

  • Shinya MiyagishimaEmail author


Cell division in several lineages of eukaryotic algae occurs predominantly during the night. Cell cycle progression is shown to be regulated by circadian rhythms. However, the advantages and their underlying mechanisms conferred by this restriction of cell division to night are poorly understood. By using the unicellular red alga Cyanidioschyzon merolae, we recently showed that the retinoblastoma (RB)-E2F-DP pathway inhibits G1/S transition during the daytime. In C. merolae, E2F is phosphorylated in a time-dependent manner, peaking during the evening, which in turn permits the phosphorylation of RB only when the cell has grown to a certain size threshold. In addition, it is suggested that temporal segregation of photosynthesis during the daytime, which produces reactive oxygen species (ROS), and DNA replication and mitosis during the night is important for eukaryotic algae. Because the temporal segregation of respiratory activity and cell cycle progression has been observed in yeasts and mammalian cells, the temporal restriction of cell cycle progression is probably important for facilitating the safe multiplication of eukaryotic cells.


Cell cycle Circadian rhythms Cyanidioschyzon merolae G1/S transition Retinoblastoma Synchronous culture 



Our study was partly supported by Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research 25251039 (to S.M.) and by the Core Research for Evolutional Science and Technology Program of the Japan Science and Technology Agency (to S.M.).


  1. Apel K, Hirt H (2004) Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annu Rev Plant Biol 55:373–399CrossRefPubMedGoogle Scholar
  2. Chen Z, Odstrcil EA et al (2007) Restriction of DNA replication to the reductive phase of the metabolic cycle protects genome integrity. Science 316:1916–1919CrossRefPubMedGoogle Scholar
  3. Dodd AN, Salathia N et al (2005) Plant circadian clocks increase photosynthesis, growth, survival, and competitive advantage. Science 309:630–633CrossRefPubMedGoogle Scholar
  4. Fang SC, Umen JG (2008) A suppressor screen in chlamydomonas identifies novel components of the retinoblastoma tumor suppressor pathway. Genetics 178:1295–1310CrossRefPubMedPubMedCentralGoogle Scholar
  5. Fang SC, de los Reyes C et al (2006) Cell size checkpoint control by the retinoblastoma tumor suppressor pathway. PLoS Genet e167:2Google Scholar
  6. Farre EM, Weise SE (2012) The interactions between the circadian clock and primary metabolism. Curr Opin Plant Biol 15:293–300CrossRefPubMedGoogle Scholar
  7. Geyfman M, Kumar V et al (2012) Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis. Proc Natl Acad Sci U S A 109:11758–11763CrossRefPubMedPubMedCentralGoogle Scholar
  8. Goto K, Johnson CH (1995) Is the cell division cycle gated by a circadian clock? The case of Chlamydomonas reinhardtii. J Cell Biol 129:1061–1069CrossRefPubMedGoogle Scholar
  9. Johnson CH (2010) Circadian clocks and cell division: what’s the pacemaker? Cell Cycle 9:3864–3873CrossRefPubMedPubMedCentralGoogle Scholar
  10. Kowalska E, Ripperger JA et al (2013) NONO couples the circadian clock to the cell cycle. Proc Natl Acad Sci U S A 110:1592–1599CrossRefPubMedGoogle Scholar
  11. Lopez-Juez E, Pyke KA (2005) Plastids unleashed: their development and their integration in plant development. Int J Dev Biol 49:557–577CrossRefPubMedGoogle Scholar
  12. Matsuo T, Yamaguchi S et al (2003) Control mechanism of the circadian clock for timing of cell division in vivo. Science 302:255–259CrossRefPubMedGoogle Scholar
  13. Matsuzaki M, Misumi O et al (2004) Genome sequence of the ultrasmall unicellular red alga Cyanidioschyzon merolae 10D. Nature 428:653–657CrossRefPubMedGoogle Scholar
  14. McClung CR (2006) Plant circadian rhythms. Plant Cell 18:792–803CrossRefPubMedPubMedCentralGoogle Scholar
  15. Miyagishima SY, Fujiwara T et al (2014) Translation-independent circadian control of the cell cycle in a unicellular photosynthetic eukaryote. Nat Commun 5:3807CrossRefPubMedGoogle Scholar
  16. Mori T, Johnson CH (2000) Circadian control of cell division in unicellular organisms. Prog Cell Cycle Res 4:185–192CrossRefPubMedGoogle Scholar
  17. Moriyama T, Terasawa K et al (2010) Characterization of cell-cycle-driven and light-driven gene expression in a synchronous culture system in the unicellular rhodophyte Cyanidioschyzon merolae. Microbiology 156:1730–1737CrossRefPubMedGoogle Scholar
  18. Moulager M, Monnier A et al (2007) Light-dependent regulation of cell division in Ostreococcus: evidence for a major transcriptional input. Plant Physiol 144:1360–1369CrossRefPubMedPubMedCentralGoogle Scholar
  19. Moulager M, Corellou F et al (2010) Integration of light signals by the retinoblastoma pathway in the control of S phase entry in the picophytoplanktonic cell Ostreococcus. PLoS Genet 6:e1000957CrossRefPubMedPubMedCentralGoogle Scholar
  20. Olson BJ, Oberholzer M et al (2010) Regulation of the Chlamydomonas cell cycle by a stable, chromatin-associated retinoblastoma tumor suppressor complex. Plant Cell 22:3331–3347CrossRefPubMedPubMedCentralGoogle Scholar
  21. Tamiya H, Iwamura T et al (1953) Correlation between photosynthesis and light-independent metabolism in the growth of Chlorella. Biochim Biophys Acta 12:23–40CrossRefPubMedGoogle Scholar
  22. Trimarchi JM, Lees JA (2002) Sibling rivalry in the E2F family. Nat Rev Mol Cell Biol 3:11–20CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Department of Cell GeneticsNational Institute of GeneticsShizuokaJapan

Personalised recommendations