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CDC45  -  Cdc45p

Saccharomyces cerevisiae S288c

Synonyms: Cell division control protein 45, L8004.11, SLD4, YLR103C
 
 
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Disease relevance of CDC45

 

High impact information on CDC45

 

Biological context of CDC45

 

Anatomical context of CDC45

  • We cloned four and one species of the human Cdc45p homolog cDNA, resulting from different splicing patterns, from HeLa cell and human placenta cDNA libraries, respectively [11].
  • In addition we show that a stoichiometric mcm interaction may not be obligatory for the function of cdc45 in follicle cell replication, because, unlike the mcm proteins, DmCdc45 localises to the chorion amplification foci in the follicle cells of the ovary [12].
  • Evidence is also provided that Pol epsilon holoenzyme interacts directly with GINS, Cdc45p and Cut5p, each of which plays an important role in initiation of chromosomal DNA replication in eukaryotic cells [13].
 

Physical interactions of CDC45

  • Cdc45p assembles into a complex with Cdc46p/Mcm5p, is required for minichromosome maintenance, and is essential for chromosomal DNA replication [14].
  • Cdc45p is also shown to interact with Cdc47p in vivo and to be a component of high-molecular-weight MCM complexes in cell lysates [15].
  • Mcm10p functionally interacts with components of the pre-replicative complex (Mcm2-Mcm7 complex and origin recognition complex) as well as the pre-initiation complex component (Cdc45p) suggesting that it may be a component of the pre-RC as well as the pre-IC [16].
  • Deletion of RPD3 histone deacetylase causes earlier origin firing and concurrent binding of the replication factor Cdc45p to origins [17].
  • Here we show that both Cdc45p and replication protein A (RPA) bind to Mcm2p at the G(1)-S transition in an S-CDK-dependent manner [18].
 

Regulatory relationships of CDC45

  • These findings suggest that S-CDKs and Cdc7p-Dbf4p promote loading of Cdc45p and RPA onto a preformed prereplication complex at each origin with preprogrammed timing [18].
  • Fission yeast Cdc23/Mcm10 functions after pre-replicative complex formation to promote Cdc45 chromatin binding [19].
 

Other interactions of CDC45

  • We investigated this possibility further and present evidence demonstrating that Cdc45p is assembled into complexes with one MCM family member, Cdc46p/Mcm5p [14].
  • Characterization of Cdc47p-minichromosome maintenance complexes in Saccharomyces cerevisiae: identification of Cdc45p as a subunit [15].
  • A role for the replication proteins PCNA, RF-C, polymerase epsilon and Cdc45 in transcriptional silencing in Saccharomyces cerevisiae [9].
  • Here we show that both an allele of CDC45 (JET1) and high-copy DPB11, in combination with Sld2-11D, separately confer CDK-independent DNA replication [20].
  • In addition, Cdc45p and Cdc7p/Dbf4p, a kinase implicated in the G1/S phase transition, are dependent on one another for function [7].
 

Analytical, diagnostic and therapeutic context of CDC45

References

  1. Requirement of CDC45 for postimplantation mouse development. Yoshida, K., Kuo, F., George, E.L., Sharpe, A.H., Dutta, A. Mol. Cell. Biol. (2001) [Pubmed]
  2. A requirement for MCM7 and Cdc45 in chromosome unwinding during eukaryotic DNA replication. Pacek, M., Walter, J.C. EMBO J. (2004) [Pubmed]
  3. Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase. Aparicio, O.M., Weinstein, D.M., Bell, S.P. Cell (1997) [Pubmed]
  4. Formation of a preinitiation complex by S-phase cyclin CDK-dependent loading of Cdc45p onto chromatin. Zou, L., Stillman, B. Science (1998) [Pubmed]
  5. GINS, a novel multiprotein complex required for chromosomal DNA replication in budding yeast. Takayama, Y., Kamimura, Y., Okawa, M., Muramatsu, S., Sugino, A., Araki, H. Genes Dev. (2003) [Pubmed]
  6. A novel ring-like complex of Xenopus proteins essential for the initiation of DNA replication. Kubota, Y., Takase, Y., Komori, Y., Hashimoto, Y., Arata, T., Kamimura, Y., Araki, H., Takisawa, H. Genes Dev. (2003) [Pubmed]
  7. CDC45 is required in conjunction with CDC7/DBF4 to trigger the initiation of DNA replication. Owens, J.C., Detweiler, C.S., Li, J.J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  8. CDC45, a novel yeast gene that functions with the origin recognition complex and Mcm proteins in initiation of DNA replication. Zou, L., Mitchell, J., Stillman, B. Mol. Cell. Biol. (1997) [Pubmed]
  9. A role for the replication proteins PCNA, RF-C, polymerase epsilon and Cdc45 in transcriptional silencing in Saccharomyces cerevisiae. Ehrenhofer-Murray, A.E., Kamakaka, R.T., Rine, J. Genetics (1999) [Pubmed]
  10. Identification of Cdc45p, an essential factor required for DNA replication. Hardy, C.F. Gene (1997) [Pubmed]
  11. Human CDC45 protein binds to minichromosome maintenance 7 protein and the p70 subunit of DNA polymerase alpha. Kukimoto, I., Igaki, H., Kanda, T. Eur. J. Biochem. (1999) [Pubmed]
  12. Localisation of the DmCdc45 DNA replication factor in the mitotic cycle and during chorion gene amplification. Loebel, D., Huikeshoven, H., Cotterill, S. Nucleic Acids Res. (2000) [Pubmed]
  13. The DNA polymerase activity of Pol epsilon holoenzyme is required for rapid and efficient chromosomal DNA replication in Xenopus egg extracts. Shikata, K., Sasa-Masuda, T., Okuno, Y., Waga, S., Sugino, A. BMC Biochem. (2006) [Pubmed]
  14. Cdc45p assembles into a complex with Cdc46p/Mcm5p, is required for minichromosome maintenance, and is essential for chromosomal DNA replication. Hopwood, B., Dalton, S. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  15. Characterization of Cdc47p-minichromosome maintenance complexes in Saccharomyces cerevisiae: identification of Cdc45p as a subunit. Dalton, S., Hopwood, B. Mol. Cell. Biol. (1997) [Pubmed]
  16. Budding yeast mcm10/dna43 mutant requires a novel repair pathway for viability. Araki, Y., Kawasaki, Y., Sasanuma, H., Tye, B.K., Sugino, A. Genes Cells (2003) [Pubmed]
  17. Histone acetylation regulates the time of replication origin firing. Vogelauer, M., Rubbi, L., Lucas, I., Brewer, B.J., Grunstein, M. Mol. Cell (2002) [Pubmed]
  18. Assembly of a complex containing Cdc45p, replication protein A, and Mcm2p at replication origins controlled by S-phase cyclin-dependent kinases and Cdc7p-Dbf4p kinase. Zou, L., Stillman, B. Mol. Cell. Biol. (2000) [Pubmed]
  19. Fission yeast Cdc23/Mcm10 functions after pre-replicative complex formation to promote Cdc45 chromatin binding. Gregan, J., Lindner, K., Brimage, L., Franklin, R., Namdar, M., Hart, E.A., Aves, S.J., Kearsey, S.E. Mol. Biol. Cell (2003) [Pubmed]
  20. CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast. Tanaka, S., Umemori, T., Hirai, K., Muramatsu, S., Kamimura, Y., Araki, H. Nature (2007) [Pubmed]
  21. Sld3, which interacts with Cdc45 (Sld4), functions for chromosomal DNA replication in Saccharomyces cerevisiae. Kamimura, Y., Tak, Y.S., Sugino, A., Araki, H. EMBO J. (2001) [Pubmed]
 
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