Calmodulin is involved in the induction of DNA polymerases alpha and delta activities in normal rat kidney cells activated to proliferate.
Normal rat kidney cells that reenter the cell cycle from quiescence start DNA synthesis at 12 h following serum addition and reach a maximum after 20 h. We have previously shown that the activation of DNA polymerase alpha, and the expression of the proliferating cell nuclear antigen were inhibited when the anti-calmodulin drug W13 is added to the cell cultures. Here we have analyzed the effect of W13 on the activity of DNA polymerase delta and on the expression of replication protein A. The results showed that the blockade of calmodulin by W13 produced an almost complete inhibition of DNA polymerase delta activity whereas the activity of DNA polymerase alpha was only partially inhibited. Finally, the expression of replication protein A was not affected after W13 treatment. Our data suggest that calmodulin might regulate DNA replication through the control of the activities of DNA polymerases alpha and delta and the expression of proliferating cell nuclear antigen.
López-Girona
A
A
Departament de Biologia Cel.lular, Facultat de Medicina, Universitat de Barcelona, Spain.
Bachs
O
O
Agell
N
N
D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D002455:Cell Division; D002478:Cells, Cultured; D004257:DNA Polymerase II / Q000378:metabolism*; D004258:DNA Polymerase III; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D004790:Enzyme Induction; D016193:G1 Phase; D007668:Kidney / Q000166:cytology* / Q000201:enzymology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D051716:Replication Protein A; D013449:Sulfonamides / Q000494:pharmacology
D002147:Calmodulin; D004268:DNA-Binding Proteins; D018809:Proliferating Cell Nuclear Antigen; D051716:Replication Protein A; D013449:Sulfonamides; C040184:W 12; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide; D004257:DNA Polymerase II; D004258:DNA Polymerase III; D004259:DNA-Directed DNA Polymerase