Interactions of human Cdc45 with the Mcm2-7 complex, the GINS complex, and DNA polymerases delta and epsilon during S phase.
Cdc45 is an essential cellular protein that functions in both the initiation and elongation of DNA replication. Here, we analyzed the localization of human Cdc45 and its interactions with other proteins during the cell cycle. Human Cdc45 showed a diffuse distribution in G1 phase, a spot-like pattern in S and G2, and again a diffuse distribution in M phase of the cell cycle. The co-localization of Cdc45 with active replication sites during S phase suggested that the human Cdc45 protein was part of the elongation complex. This view was corroborated by findings that Cdc45 interacted with the elongating DNA polymerases delta and epsilon, with Psf2, which is a component of the GINS complex as well as with Mcm5 and 7, subunits of the putative replicative DNA helicase complex. Hence, Cdc45 may play an important role in elongation of DNA replication by bridging the processive DNA polymerases delta and epsilon with the replicative helicase in the elongating machinery.
Bauerschmidt
Christina
C
Biochemistry Group, Leibniz Institute for Age Research-Fritz-Lipmann-Institute e. V., Beutenbergstrasse 11, D-07745 Jena, Germany.
Pollok
Sibyll
S
Kremmer
Elisabeth
E
Nasheuer
Heinz-Peter
HP
Grosse
Frank
F
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000737:chemistry; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004257:DNA Polymerase II / Q000378:metabolism*; D004258:DNA Polymerase III / Q000737:chemistry*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D064111:Minichromosome Maintenance Complex Component 2; D064168:Minichromosome Maintenance Complex Component 7; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D016196:S Phase
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000911:Antibodies, Monoclonal; C113571:CDC45 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C489423:MCM5 protein, human; D009687:Nuclear Proteins; C071692:TAP2 protein, human; D004257:DNA Polymerase II; D004258:DNA Polymerase III; C084859:MCM2 protein, human; C101624:MCM7 protein, human; D064111:Minichromosome Maintenance Complex Component 2; D064168:Minichromosome Maintenance Complex Component 7