Control of Cell Nuclear DNA Replication by Chloroplast and Mitochondrion

  • Yuki Kobayashi
  • Yu Kanesaki
  • Mitsumasa Hanaoka
  • Kan TanakaEmail author


α-Proteobacteria and cyanobacteria endosymbiosis has been crucial to the evolution of eukaryotic cells. The descendants of these bacteria gave rise to mitochondria and chloroplasts, and these organelles still retain their own genome proliferation systems. Coordination between the proliferation processes of these organelles and the eukaryotic cell cycle is indispensable for cellular maintenance, and we have studied this using the red alga Cyanidioschyzon merolae. During the cell cycle progression of C. merolae, organelle DNA replication (ODR) in both of the mitochondrion and the chloroplast occurs prior to nuclear DNA replication (NDR). We found that Mg-protoporphyrin IX (Mg-ProtoIX), a type of tetrapyrrole synthesized in the chloroplast, accumulates with the onset of ODR, thereby inducing NDR. Binding of the F-box protein Fbx3 to Mg-ProtoIX was also shown to be involved in the polyubiquitination of Cyclin 1, which activates cyclin-dependent kinase. Moreover, Mg-ProtoIX–Fbx3 binding inhibits Fbx3-mediated polyubiquitination of Cyclin 1. These results suggest that Fbx3 is a receptor for Mg-ProtoIX in the chloroplast signal to the nucleus and that it appears to function as a checkpoint for the coordination of ODR and NDR. In this chapter, we discuss the ODR and NDR coordination system in the cell cycle.


Cell cycle DNA replication Endosymbiosis Evolution Organelle Retrograde signal Tetrapyrrole Ubiquitination 


  1. Dharmasiri N, Dharmasiri S, Estelle M (2005) The F-box protein TIR1 is an auxin receptor. Nature 435(7041):441–445CrossRefPubMedGoogle Scholar
  2. Ekholm SV, Reed SI (2000) Regulation of G1 cyclin-dependent kinases in the mammalian cell cycle. Curr Opin Cell Biol 12(6):676–684CrossRefPubMedGoogle Scholar
  3. Fujiwara T, Ohnuma M, Yoshida M et al (2013) Gene targeting in the red alga Cyanidioschyzon merolae: single- and multi-copy insertion using authentic and chimeric selection markers. PLoS One 8:e73608CrossRefPubMedPubMedCentralGoogle Scholar
  4. Gough NR (2009) Wait for me. Sci Signal 2(55):ec27Google Scholar
  5. Gray MW (1993) Origin and evolution of organelle genomes. Curr Opin Genet Dev 3(6):884–890CrossRefPubMedGoogle Scholar
  6. Hartung W (2010) The evolution of abscisic acid (ABA) and ABA function in lower plants, fungi and lichen. Func Plant Biol 37(9):806–812CrossRefGoogle Scholar
  7. Hauser F, Waadt R, Schroeder JI (2011) Evolution of abscisic acid synthesis and signaling mechanisms. Curr Biol 21(9):R346–R355CrossRefPubMedPubMedCentralGoogle Scholar
  8. Jung T, Catalgol B, Grune T (2009) The proteasomal system. Mol Asp Med 30(4):191–296CrossRefGoogle Scholar
  9. Kepinski S, Leyser O (2005) The Arabidopsis F-box TIR1 is an auxin receptor. Nature 435(7041):446–451CrossRefPubMedGoogle Scholar
  10. Kobayashi Y, Kanesaki Y, Tanaka A et al (2009) Tetrapyrrole signal as a cell-cycle coordinator from organelle to nuclear DNA replication in plant cells. Proc Natl Acad Sci U S A 106(3):803–807CrossRefPubMedPubMedCentralGoogle Scholar
  11. Kobayashi Y, Ohnuma M, Kuroiwa T et al (2010) The basics of cultivation and molecular genetic analysis of the unicellular red alga Cyanidioschyzon merolae. Endocytobiosis Cell Res 20:53–61Google Scholar
  12. Kobayashi Y, Imamura S, Hanaoka S et al (2011) A tetrapyrrole-regulated ubiquitin ligase controls algal nuclear DNA replication. Nat Cell Biol 13(4):483–487CrossRefPubMedGoogle Scholar
  13. Kobayashi Y, Ando H, Hanaoka M et al (2016) Abscisic acid participates in the control of cell-cycle initiation through heme homeostasis in the unicellular red alga Cyanidioschyzon merolae. Plant Cell Physiol 57(5):953–960CrossRefPubMedGoogle Scholar
  14. Kuroiwa T (1998) The primitive red algae: Cyanidium caldarium and Cyanidioschyzon merolae as model system for investigating the dividing apparatus of mitochondria and plastids. BioEssays 20(4):344–354CrossRefGoogle Scholar
  15. Kuroiwa T (2004) Organelle nuclei in higher plants: structure, composition, function, and evolution. Int Rev Cytol 238:59–117CrossRefPubMedGoogle Scholar
  16. Leister D (2005) Genomics-based dissection of the cross-talk of chloroplasts with the nucleus and mitochondria in Arabidopsis. Gene 354:110–116CrossRefPubMedGoogle Scholar
  17. Matsuzaki M, Misumi O, Shin-I T et al (2004) Genome sequence of the ultrasmall unicellular red alga Cyanidioschyzon merolae 10D. Nature 428(6983):653–657CrossRefPubMedGoogle Scholar
  18. Mense SM, Zhang L (2006) Heme: a versatile signaling molecule controlling the activities of diverse regulators ranging from transcription factors to MAP kinase. Cell Res 16(8):681–692CrossRefPubMedGoogle Scholar
  19. Nott A, Jung H, Koussevitzky S et al (2006) Plastid-to-nucleus retrograde signaling. Annu Rev Plant Biol 57:739–759CrossRefPubMedGoogle Scholar
  20. Nozaki H, Takano H, Misumi O et al (2007) A 100%-complete sequence reveals unusually simple genomic features in the hot spring red alga Cyanidioschyzon merolae. BMC Biol 5:28CrossRefPubMedPubMedCentralGoogle Scholar
  21. Ohta N, Sato N, Kuroiwa T (1998) Structure and organization of the mitochondrial genome of the unicellular red alga Cyanidioschyzon merolae deduced from the complete nucleotide sequence. Nucleic Acids Res 26(22):5190–5198CrossRefPubMedPubMedCentralGoogle Scholar
  22. Ohta N, Matsuzaki M, Misumi O et al (2003) Complete sequence and analysis of the plastid genome of the unicellular red alga Cyanidioschyzon merolae. DNA Res 10(2):67–77CrossRefPubMedGoogle Scholar
  23. Palenik B (1992) Polymerase evolution and organism evolution. Curr Opin Genet Dev 2(6):931–936CrossRefPubMedGoogle Scholar
  24. Reed SI (2006) The ubiquitin proteasome pathway in cell cycle control. Results Probl Cell Differ 42:147–181CrossRefPubMedGoogle Scholar
  25. Sakai A, Takano H, Kuroiwa T (2004) Organelle nuclei in higher plants: structure, composition, function, and evolution. Int Rev Cytol 238:59–117CrossRefPubMedGoogle Scholar
  26. Somers DE, Fujiwara S (2009) Thinking outside the F-box: novel ligands for novel receptors. Trends Plant Sci 14(4):206–213CrossRefPubMedGoogle Scholar
  27. Suzuki K, Ehara T, Osafune T et al (1994) Behavior of mitochondria, chloroplasts and their nuclei during the mitotic cycle in the ultramicroalga Cyanidioschyzon merolae. Eur J Cell Biol 63(2):280–288PubMedGoogle Scholar
  28. Watanabe S, Hanaoka M, Ohba Y et al (2013) Mitochondrial localization of ferrochelatase in a red alga Cyanidioschyzon merolae. Plant Cell Physiol 54(8):1289–1295CrossRefPubMedGoogle Scholar
  29. Zegerman P, Diffley JF (2007) Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast. Nature 445(7125):281–285CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  • Yuki Kobayashi
    • 1
  • Yu Kanesaki
    • 2
  • Mitsumasa Hanaoka
    • 3
  • Kan Tanaka
    • 1
    Email author
  1. 1.Laboratory for Chemistry and Life Science, Institute of Innovative ResearchTokyo Institute of TechnologyYokohamaJapan
  2. 2.Research Institute of Green Science and TechnologyShizuoka UniversityShizuokaJapan
  3. 3.Graduate School of HorticultureChiba UniversityChibaJapan

Personalised recommendations