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Gene Review

CDC45  -  cell division cycle 45

Homo sapiens

Synonyms: CDC45L, CDC45L2, Cell division control protein 45 homolog, PORC-PI-1, UNQ374/PRO710
 
 
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Disease relevance of CDC45L

 

Psychiatry related information on CDC45L

 

High impact information on CDC45L

  • Genetic evidence suggests that phosphorylation of Mcm4 by DDK is important for timely S phase progression and for cell viability upon overproduction of Cdc45 [3].
  • MCPH1-mutant and ATR-Seckel cells also show impaired degradation of Cdc25A and fail to inhibit Cdc45 loading onto chromatin after replication arrest [4].
  • GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks [5].
  • RPC components include the essential initiation and elongation factor, Cdc45, the checkpoint mediator Mrc1, the Tof1-Csm3 complex that allows replication forks to pause at protein-DNA barriers, the histone chaperone FACT (facilitates chromatin transcription) and Ctf4, which helps to establish sister chromatid cohesion [5].
  • Ordered assembly of Sld3, GINS and Cdc45 is distinctly regulated by DDK and CDK for activation of replication origins [6].
 

Biological context of CDC45L

 

Associations of CDC45L with chemical compounds

 

Regulatory relationships of CDC45L

  • The levels of chromatin-associated Cdc45 (but not soluble Cdc45) were reduced concomitantly with BPDE-induced Chk1 activation and inhibition of DNA synthesis [9].
 

Other interactions of CDC45L

 

Analytical, diagnostic and therapeutic context of CDC45L

References

  1. The human homolog of Saccharomyces cerevisiae CDC45. Saha, P., Thome, K.C., Yamaguchi, R., Hou, Z., Weremowicz, S., Dutta, A. J. Biol. Chem. (1998) [Pubmed]
  2. Characterization of CDC45L: a gene in the 22q11.2 deletion region expressed during murine and human development. Shaikh, T.H., Gottlieb, S., Sellinger, B., Chen, F., Roe, B.A., Oakey, R.J., Emanuel, B.S., Budarf, M.L. Mamm. Genome (1999) [Pubmed]
  3. Cdc7-Dbf4 Phosphorylates MCM Proteins via a Docking Site-Mediated Mechanism to Promote S Phase Progression. Sheu, Y.J., Stillman, B. Mol. Cell (2006) [Pubmed]
  4. Regulation of mitotic entry by microcephalin and its overlap with ATR signalling. Alderton, G.K., Galbiati, L., Griffith, E., Surinya, K.H., Neitzel, H., Jackson, A.P., Jeggo, P.A., O'Driscoll, M. Nat. Cell Biol. (2006) [Pubmed]
  5. GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks. Gambus, A., Jones, R.C., Sanchez-Diaz, A., Kanemaki, M., van Deursen, F., Edmondson, R.D., Labib, K. Nat. Cell Biol. (2006) [Pubmed]
  6. Ordered assembly of Sld3, GINS and Cdc45 is distinctly regulated by DDK and CDK for activation of replication origins. Yabuuchi, H., Yamada, Y., Uchida, T., Sunathvanichkul, T., Nakagawa, T., Masukata, H. EMBO J. (2006) [Pubmed]
  7. 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]
  8. Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage. Syljuåsen, R.G., Sørensen, C.S., Hansen, L.T., Fugger, K., Lundin, C., Johansson, F., Helleday, T., Sehested, M., Lukas, J., Bartek, J. Mol. Cell. Biol. (2005) [Pubmed]
  9. The Chk1-mediated S-phase Checkpoint Targets Initiation Factor Cdc45 via a Cdc25A/Cdk2-independent Mechanism. Liu, P., Barkley, L.R., Day, T., Bi, X., Slater, D.M., Alexandrow, M.G., Nasheuer, H.P., Vaziri, C. J. Biol. Chem. (2006) [Pubmed]
  10. The CLDN5 locus may be involved in the vulnerability to schizophrenia. Sun, Z.Y., Wei, J., Xie, L., Shen, Y., Liu, S.Z., Ju, G.Z., Shi, J.P., Yu, Y.Q., Zhang, X., Xu, Q., Hemmings, G.P. Eur. Psychiatry (2004) [Pubmed]
  11. UFD1L and CDC45L: a role in DiGeorge syndrome and related phenotypes? Novelli, G., Amati, F., Dallapiccola, B. Trends Genet. (1999) [Pubmed]
  12. Chromatin decondensation in S-phase involves recruitment of Cdk2 by Cdc45 and histone H1 phosphorylation. Alexandrow, M.G., Hamlin, J.L. J. Cell Biol. (2005) [Pubmed]
 
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