Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Dbf4

  • Hisao Masai
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_186

Synonyms

Historical Background

dbf4 (dumbbell former 4) mutation was originally identified in the screening for budding yeast temperature-sensitive mutants which arrest with dumbbell-shaped phenotype at the nonpermissive temperature (Johnston and Thomas 1982). The terminal phenotypes of dbf4(ts) strain at a non-permissive temperature were very similar to those of cdc7 (ts), encoding a serine-threonine kinase known to be essential for initiation of DNA replication. Later, dbf4 was rediscovered as a multi-copy suppressor of cdc7(ts), suggesting physical and functional interactions between Cdc7 and Dbf4 (Kitada et al. 1992). Following this finding, Dbf4 was shown to bind to...

This is a preview of subscription content, log in to check access.

References

  1. Brott BK, Sokol SY. A vertebrate homolog of the cell cycle regulator Dbf4 is an inhibitor of Wnt signaling required for heart development. Dev Cell. 2005;8(5):703–15.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Brown GW, Kelly TJ. Purification of Hsk1, a minichromosome maintenance protein kinase from fission yeast. J Biol Chem. 1998;273(34):22083–90.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Brown GW, Kelly TJ. Cell cycle regulation of Dfp1, an activator of the Hsk1 protein kinase. Proc Natl Acad Sci USA. 1999;96(15):8443–8.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Chapman JW, Johnston LH. The yeast gene, DBF4, essential for entry into S phase is cell cycle regulated. Exp Cell Res. 1989;180(2):419–28.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Chen YC, Kenworthy J, Gabrielse C, Hänni C, Zegerman P, Weinreich M. DNA replication checkpoint signaling depends on a Rad53-Dbf4 N-terminal interaction in Saccharomyces cerevisiae. Genetics. 2013;194(2):389–401.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Dowell SJ, Romanowski P, Diffley JF. Interaction of Dbf4, the Cdc7 protein kinase regulatory subunit, with yeast replication origins in vivo. Science. 1994;265(5176):1243–6.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Ferreira MF, Santocanale C, Drury LS, Diffley JF. Dbf4p, an essential S phase-promoting factor, is targeted for degradation by the anaphase-promoting complex. Mol Cell Biol. 2000;20(1):242–8.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Fung AD, Ou J, Bueler S, Brown GW. A conserved domain of Schizosaccharomyces pombe dfp1(+) is uniquely required for chromosome stability following alkylation damage during S phase. Mol Cell Biol. 2002;22(13):4477–90.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Harkins V, Gabrielse C, Haste L, Weinreich M. Budding yeast Dbf4 sequences required for Cdc7 kinase activation and identification of a functional relationship between the Dbf4 and Rev1 BRCT domains. Genetics. 2009;183(4):1269–82.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Heffernan TP, Unsal-Kaçmaz K, Heinloth AN, Simpson DA, Paules RS, Sancar A, Cordeiro-Stone M, Kaufmann WK. Cdc7-Dbf4 and the human S checkpoint response to UVC. J Biol Chem. 2007;282(13):9458–68.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Hughes S, Jenkins V, Dar MJ, Engelman A, Cherepanov P. Transcriptional co-activator LEDGF interacts with Cdc7-activator of S-phase kinase (ASK) and stimulates its enzymatic activity. J Biol Chem. 2010;285(1):541–54.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Jackson AL, Pahl PM, Harrison K, Rosamond J, Sclafani RA. Cell cycle regulation of the yeast Cdc7 protein kinase by association with the Dbf4 protein. Mol Cell Biol. 1993;13(5):2899–908.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Jiang W, McDonald D, Hope TJ, Hunter T. Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication. EMBO J. 1999; 18(20):5703–13.PubMedPubMedCentralCrossRefGoogle Scholar
  14. James SW, Bullock KA, Gygax SE, Kraynack BA, Matura RA, MacLeod JA, McNeal KK, Prasauckas KA, Scacheri PC, Shenefiel HL, Tobin HM, Wade SD. nimO, an Aspergillus gene related to budding yeast Dbf4, is required for DNA synthesis and mitotic checkpoint control. J Cell Sci. 1999;112(Pt 9):1313–24.PubMedCentralPubMedGoogle Scholar
  15. Johnston LH, Thomas AP. A further two mutants defective in initiation of the S phase in the yeast Saccharomyces cerevisiae. Mol Gen Genet. 1982;186(3):445–8.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Jones DR, Prasad AA, Chan PK, Duncker BP. The Dbf4 motif C zinc finger promotes DNA replication and mediates resistance to genotoxic stress. Cell Cycle. 2010 9(10):2018–26.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Katis VL, Lipp JJ, Imre R, Bogdanova A, Okaz E, Habermann B, Mechtler K, Nasmyth K, Zachariae W. Rec8 phosphorylation by casein kinase 1 and Cdc7-Dbf4 kinase regulates cohesin cleavage by separase during meiosis. Dev Cell. 2010;18(3):397–409.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Kitada K, Johnston LH, Sugino T, Sugino A. Temperature-sensitive cdc7 mutations of Saccharomyces cerevisiae are suppressed by the DBF4 gene, which is required for the G1/S cell cycle transition. Genetics. 1992;131(1):21–9.PubMedPubMedCentralGoogle Scholar
  19. Kitamura R, Fukatsu R, Kakusho N, Cho Y-S, Taniyama C, Yamazaki S, Toh G-T, Yanagi K, Arai N, Chang H-J, Masai H. Molecular mechanism of activation of human Cdc7 kinase: bipartite interaction with Dbf4/ASK stimulates ATP binding and substrate recognition. J Biol Chem. 2011;286:23031–43.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Kneissl M, Pütter V, Szalay AA, Grummt F. Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells. J Mol Biol. 2003;327(1):111–28.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Kumagai H, Sato N, Yamada M, Mahony D, Seghezzi W, Lees E, Arai K, Masai H. A novel growth- and cell cycle-regulated protein, ASK, activates human Cdc7-related kinase and is essential for G1/S transition in mammalian cells. Mol Cell Biol. 1999;19(7):5083–95.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Landis G, Tower J. The Drosophila chiffon gene is required for chorion gene amplification, and is related to the yeast Dbf4 regulator of DNA replication and cell cycle. Development. 1999;126(19):4281–93.PubMedCentralPubMedGoogle Scholar
  23. Lei M, Kawasaki Y, Young MR, Kihara M, Sugino A, Tye BK. Mcm2 is a target of regulation by Cdc7-Dbf4 during the initiation of DNA synthesis. Genes Dev. 1997;11(24):3365–74.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Lo HC, Wan L, Rosebrock A, Futcher B, Hollingsworth NM. Cdc7-Dbf4 regulates NDT80 transcription as well as reductional segregation during budding yeast meiosis. Mol Biol Cell. 2008;19:4956–67.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Lopez-Mosqueda J, Maas NL, Jonsson ZO, Defazio-Eli LG, Wohlschlegel J, Toczyski DP. Damage-induced phosphorylation of Sld3 is important to block late origin firing. Nature. 2010;467(7314):479–83.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Mantiero D, Mackenzie A, Donaldson A, Zegerman P. Limiting replication initiation factors execute the temporal programme of origin firing in budding yeast. EMBO J. 2011;30(23):4805–14.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Masai H, Arai K. Dbf4 motifs: conserved motifs in activation subunits for Cdc7 kinases essential for S-phase. Biochem Biophys Res Commun. 2000;275(1):228–32.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Masai H, Miyake T, Arai K. hsk1+, a Schizosaccharomyces pombe gene related to Saccharomyces cerevisiae CDC7, is required for chromosomal replication. EMBO J. 1995;14(13):3094–104.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Masai H, Matsumoto S, You Z, Yoshizawa-Sugata N, Oda M. Eukaryotic chromosome DNA replication: where, when, and how? Annu Rev Biochem. 2010;79:89–130.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Matos J, Lipp JJ, Bogdanova A, Guillot S, Okaz E, Junqueira M, Shevchenko A, Zachariae W. Dbf4-dependent CDC7 kinase links DNA replication to the segregation of homologous chromosomes in meiosis I. Cell. 2008;135(4):662–78.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Matthews LA, Selvaratnam R, Jones DR, Akimoto M, McConkey BJ, Melacini G, Duncker BP, Guarné A. A novel non-canonical forkhead-associated (FHA) domain-binding interface mediates the interaction between Rad53 and Dbf4 proteins. J Biol Chem. 2014;289(5):2589–99.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Montagnoli A, Bosotti R, Villa F, Rialland M, Brotherton D, Mercurio C, Berthelsen J, Santocanale C. Drf1, a novel regulatory subunit for human Cdc7 kinase. EMBO J. 2002;21(12):3171–81.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Nakamura T, Kishida M, Shimoda C. The Schizosaccharomyces pombe spo6+ gene encoding a nuclear protein with sequence similarity to budding yeast Dbf4 is required for meiotic second division and sporulation. Genes Cells. 2000;5(6):463–79.CrossRefPubMedGoogle Scholar
  34. Ogino K, Takeda T, Matsui E, Iiyama H, Taniyama C, Arai K, Masai H. Bipartite binding of a kinase activator activates Cdc7-related kinase essential for S phase. J Biol Chem. 2001;276(33):31376–87.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Ogino K, Hirota K, Matsumoto S, Takeda T, Ohta K, Arai K, Masai H. Hsk1 kinase is required for induction of meiotic dsDNA breaks without involving checkpoint kinases in fission yeast. Proc Natl Acad Sci USA. 2006;103(21):8131–6.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Oshiro G, Owens JC, Shellman Y, Sclafani RA, Li JJ. Cell cycle control of Cdc7p kinase activity through regulation of Dbf4p stability. Mol Cell Biol. 1999;19(7):4888–96.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Patel PK, Kommajosyula N, Rosebrock A, Bensimon A, Leatherwood J, Bechhoefer J, Rhind N. The Hsk1(Cdc7) replication kinase regulates origin efficiency. Mol Biol Cell. 2008;19(12):5550–8.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Sasanuma H, Hirota K, Fukuda T, Kakusho N, Kugou K, Kawasaki Y, Shibata T, Masai H, Ohta K. Cdc7-dependent phosphorylation of Mer2 facilitates initiation of yeast meiotic recombination. Genes Dev. 2008;22(3):398–410.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Sato N, Arai K, Masai H. Human and Xenopus cDNAs encoding budding yeast Cdc7-related kinases: in vitro phosphorylation of MCM subunits by a putative human homologue of Cdc7. EMBO J. 1997;16(14):4340–51.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Sheu YJ, Stillman B. Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression. Mol Cell. 2006;24:101–13.PubMedPubMedCentralCrossRefGoogle Scholar
  41. Snaith HA, Brown GW, Forsburg SL. Schizosaccharomyces pombe Hsk1p is a potential cds1p target required for genome integrity. Mol Cell Biol. 2000;20(21):7922–32.PubMedPubMedCentralCrossRefGoogle Scholar
  42. Takahashi TS, Walter JC. Cdc7-Drf1 is a developmentally regulated protein kinase required for the initiation of vertebrate DNA replication. Genes Dev. 2005;19(19):2295–300.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Takeda T, Ogino K, Matsui E, Cho MK, Kumagai H, Miyake T, Arai K, Masai H. A fission yeast gene, him1(+)/dfp1(+), encoding a regulatory subunit for Hsk1 kinase, plays essential roles in S-phase initiation as well as in S-phase checkpoint control and recovery from DNA damage. Mol Cell Biol. 1999;19(8):5535–47.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Takeda T, Ogino K, Tatebayashi K, Ikeda H, Ki A, Masai H. Regulation of initiation of S phase, replication checkpoint signaling, and maintenance of mitotic chromosome structures during S phase by Hsk1 kinase in the fission yeast. Mol Biol Cell. 2001;12(5):1257–74.PubMedPubMedCentralCrossRefGoogle Scholar
  45. Valentin G, Schwob E, Della SF. Dual role of the Cdc7-regulatory protein Dbf4 during yeast meiosis. J Biol Chem. 2006;281(5):2828–34.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Wan L, Niu H, Futcher B, Zhang C, Shokat KM, Boulton SJ, Hollingsworth NM. Cdc28-Clb5 (CDK-S) and Cdc7-Dbf4 (DDK) collaborate to initiate meiotic recombination in yeast. Genes Dev. 2008;22(3):386–97.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Wu X, Lee H. Human Dbf4/ASK promoter is activated through the Sp1 and MluI cell-cycle box (MCB) transcription elements. Oncogene. 2002;21(51):7786–96.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Wu PY, Nurse P. Establishing the program of origin firing during S phase in fission yeast. Cell. 2009;136(5):852–64.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Yamada M, Sato N, Taniyama C, Ohtani K, Arai K, Masai H. A 63-base pair DNA segment containing an Sp1 site but not a canonical E2F site can confer growth-dependent and E2F-mediated transcriptional stimulation of the human ASK gene encoding the regulatory subunit for human Cdc7-related kinase. J Biol Chem. 2002;277(31):27668–81.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Yamashita N, Kim JM, Koiwai O, Arai K, Masai H. Functional analyses of mouse ASK, an activation subunit for Cdc7 kinase, using conditional ASK knockout ES cells. Genes Cells. 2005;10(6):551–63.CrossRefPubMedGoogle Scholar
  51. Yoshizawa-Sugata N, Ishii A, Taniyama C, Matsui E, Arai K, Masai H. A second human Dbf4/ASK-related protein, Drf1/ASKL1, is required for efficient progression of S and M phases. J Biol Chem. 2005;280(13):13062–70.CrossRefPubMedGoogle Scholar
  52. Zegerman P, Diffley JF. Checkpoint-dependent inhibition of DNA replication initiation by Sld3 and Dbf4 phosphorylation. Nature. 2010;467(7314):474–8.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Genome Dynamics Project, Department of Genome MedicineTokyo Metropolitan Institute of Medical ScienceTokyoJapan