Nuclear localization of 68 kDa calmodulin-binding protein is associated with the onset of DNA replication.
In Chinese hamster embryo fibroblast cells, an increase in intracellular calmodulin levels coincided with the nuclear localization of a calmodulin-binding protein of about 68 kDa as the cells progressed from G1 to S phase. When cells were limited from entering into S phase, by omitting insulin a defined medium, intracellular CaM levels did not increase and the 68 kDa calmodulin-binding protein was completely absent from the nuclei. Corresponding to the nuclear localization of calmodulin and the 68 kDa calmodulin-binding protein in S phase cells, there was a dramatic increase in DNA polymerase and thymidine kinase activities in the nuclei of S phase cells as compared to G1 phase cells. In addition, the 68 kDa calmodulin-binding protein, along with calmodulin, is observed to be an integral component of replitase complex responsible for nuclear DNA replication in S phase cells. These observations point to the association of calmodulin and calmodulin-binding protein(s) with the replication machinery responsible for nuclear DNA replication during S phase. A possible regulatory role of these proteins in the onset of DNA replication and cell proliferation is discussed.
Department of Obstetrics and Gynecology, University of Virginia Diabetes Center, Charlottesville 22906.
C
C
Subramanyam
S C
SC
Honn
W C
WC
Reed
G P
GP
Reddy
D000818:Animals; D012103:Batroxobin / Q000032:analysis / Q000378:metabolism; D002147:Calmodulin / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D002148:Calmodulin-Binding Proteins / Q000032:analysis* / Q000378:metabolism / Q000502:physiology; D002467:Cell Nucleus / Q000032:analysis* / Q000648:ultrastructure; D002478:Cells, Cultured; D006224:Cricetinae / Q000196:embryology*; D003412:Cricetulus / Q000196:embryology*; D004261:DNA Replication / Q000502:physiology*; D005347:Fibroblasts / Q000032:analysis* / Q000166:cytology / Q000648:ultrastructure; D007328:Insulin / Q000494:pharmacology; D007399:Interphase / Q000502:physiology; D007532:Isoleucine / Q000378:metabolism / Q000502:physiology
D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D007328:Insulin; D007532:Isoleucine; D012103:Batroxobin