CDC45-related protein explained

CDC45 is a protein that in humans is encoded by the CDC45L gene.^{[1] [2] [3] [4]}

Function

The protein encoded by this gene was identified by its strong similarity with Saccharomyces cerevisiae Cdc45, an essential protein required to the initiation of DNA replication. Cdc45 is a member of the highly conserved multiprotein complex including Cdc6/Cdc18, the minichromosome maintenance proteins (MCMs) and DNA polymerase, which is important for early steps of DNA replication in eukaryotes. This protein has been shown to interact with MCM7 and DNA polymerase alpha. Studies of the similar gene in Xenopus suggested that this protein plays a pivotal role in the loading of DNA polymerase alpha onto chromatin. Multiple polyadenylation sites of this gene are reported.

Interactions

CDC45-related protein has been shown to interact with:

• MCM3,
• MCM6,
• MCM7,^[5]
• ORC1L,^[6] and
• ORC6L.^[6]

Further reading

• Leatherwood J . Emerging mechanisms of eukaryotic DNA replication initiation . Curr. Opin. Cell Biol. . 10 . 6 . 742–8 . 1998 . 9914182 . 10.1016/S0955-0674(98)80117-8 .
• Mimura S, Takisawa H . Xenopus Cdc45-dependent loading of DNA polymerase alpha onto chromatin under the control of S-phase Cdk . EMBO J. . 17 . 19 . 5699–707 . 1998 . 9755170 . 1170898 . 10.1093/emboj/17.19.5699 .
• Shaikh TH, Gottlieb S, Sellinger B, Chen F, Roe BA, Oakey RJ, Emanuel BS, Budarf ML . Characterization of CDC45L: a gene in the 22q11.2 deletion region expressed during murine and human development . Mamm. Genome . 10 . 3 . 322–6 . 1999 . 10051334 . 10.1007/s003359900996 . 1653743 .
• Kukimoto I, Igaki H, Kanda T . Human CDC45 protein binds to minichromosome maintenance 7 protein and the p70 subunit of DNA polymerase alpha . Eur. J. Biochem. . 265 . 3 . 936–43 . 1999 . 10518787 . 10.1046/j.1432-1327.1999.00791.x . free .
• 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. . 327 . 1 . 111–28 . 2003 . 12614612 . 10.1016/S0022-2836(03)00079-2 .
• Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A . The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment . Genome Res. . 13 . 10 . 2265–70 . 2003 . 12975309 . 403697 . 10.1101/gr.1293003 .
• Ramachandran N, Hainsworth E, Bhullar B, Eisenstein S, Rosen B, Lau AY, Walter JC, LaBaer J . Self-assembling protein microarrays . Science . 305 . 5680 . 86–90 . 2004 . 15232106 . 10.1126/science.1097639 . 2004Sci...305...86R . 20936301 .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Liu P, Barkley LR, Day T, Bi X, Slater DM, Alexandrow MG, Nasheuer HP, Vaziri C . The Chk1-mediated S-phase checkpoint targets initiation factor Cdc45 via a Cdc25A/Cdk2-independent mechanism . J. Biol. Chem. . 281 . 41 . 30631–44 . 2006 . 16912045 . 10.1074/jbc.M602982200 . free .
• Masai H, Taniyama C, Ogino K, Matsui E, Kakusho N, Matsumoto S, Kim JM, Ishii A, Tanaka T, Kobayashi T, Tamai K, Ohtani K, Arai K . Phosphorylation of MCM4 by Cdc7 kinase facilitates its interaction with Cdc45 on the chromatin . J. Biol. Chem. . 281 . 51 . 39249–61 . 2006 . 17046832 . 10.1074/jbc.M608935200 . free .
• Boskovic J, Coloma J, Aparicio T, Zhou M, Robinson CV, Méndez J, Montoya G . Molecular architecture of the human GINS complex . EMBO Rep. . 8 . 7 . 678–84 . 2007 . 17557111 . 1905900 . 10.1038/sj.embor.7401002 .
• Bauerschmidt C, Pollok S, Kremmer E, Nasheuer HP, Grosse F . Interactions of human Cdc45 with the Mcm2-7 complex, the GINS complex, and DNA polymerases delta and epsilon during S phase . Genes Cells . 12 . 6 . 745–58 . 2007 . 17573775 . 10.1111/j.1365-2443.2007.01090.x . 41805586 . free .
• Pollok S, Grosse F . Cdc45 degradation during differentiation and apoptosis . Biochem. Biophys. Res. Commun. . 362 . 4 . 910–5 . 2007 . 17767920 . 10.1016/j.bbrc.2007.08.069 .

Notes and References

1. Saha P, Thome KC, Yamaguchi R, Hou Z, Weremowicz S, Dutta A . The human homolog of Saccharomyces cerevisiae CDC45 . J. Biol. Chem. . 273 . 29 . 18205–9 . Aug 1998 . 9660782 . 10.1074/jbc.273.29.18205 . free .
2. McKie JM, Wadey RB, Sutherland HF, Taylor CL, Scambler PJ . Direct selection of conserved cDNAs from the DiGeorge critical region: isolation of a novel CDC45-like gene . Genome Res. . 8 . 8 . 834–41 . Sep 1998 . 9724329 . 310757 . 10.1101/gr.8.8.834 .
3. Pollok S, Bauerschmidt C, Sänger J, Nasheuer HP, Grosse F . Human Cdc45 is a proliferation-associated antigen . FEBS J. . 274 . 14 . 3669–84 . Jul 2007 . 17608804 . 10.1111/j.1742-4658.2007.05900.x . free .
4. Web site: Entrez Gene: CDC45L CDC45 cell division cycle 45-like (S. cerevisiae).
5. Kukimoto I, Igaki H, Kanda T . Human CDC45 protein binds to minichromosome maintenance 7 protein and the p70 subunit of DNA polymerase alpha . Eur. J. Biochem. . 265 . 3 . 936–43 . Nov 1999 . 10518787 . 10.1046/j.1432-1327.1999.00791.x. free .
6. 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. . 327 . 1 . 111–28 . Mar 2003 . 12614612 . 10.1016/s0022-2836(03)00079-2.