| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print August 13, 2001
J. Biol. Chem, 10.1074/jbc.M104975200
Submitted on May 31, 2001
Revised on August 13, 2001
Accepted on August 10, 2001
Biochemie, Institut für Molekulare Biotechnologie, Jena, Thüringen D-07745
Corresponding Author: nasheuer{at}imb-jena.de
DNA polymerase alpha-primase (pol-prim) is the only enzyme that can start DNA replication de novo. The 180 kDa (p180) and 68 kDa (p68) subunits of the human four-subunit enzyme are phosphorylated by Cyclin-dependent kinases (Cdks) in a cell cycle-dependent manner. Cyclin A-Cdk2 physically interacts with pol-prim and phosphorylates N-terminal amino acids of the p180 and the p68 subunits, leading to an inhibition of pol-prim in initiating cell-free SV40 DNA replication. Mutation of conserved putative Cdk phosphorylation sites in the N-terminus of human p180 and p68 reduced their phosphorylation by Cyclin A-Cdk2 in vitro. In contrast to wild-type pol-prim these mutants were no longer inhibited by Cyclin A-Cdk2 in the initiation of viral DNA replication. Importantly, rather than inhibiting it, Cyclin A-Cdk2 stimulated the initiation activity of pol-prim containing a triple N-terminal alanine mutant of the p180 subunit. Together these results suggest that Cyclin A-Cdk2 executes both stimulatory and inhibitory effects on the activity of pol-prim in initiating DNA replication.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  B. E. Weiner, H. Huang, B. M. Dattilo, M. J. Nilges, E. Fanning, and W. J. Chazin An Iron-Sulfur Cluster in the C-terminal Domain of the p58 Subunit of Human DNA Primase J. Biol. Chem., November 16, 2007; 282(46): 33444 - 33451. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-J. Kim, J.-H. Kim, Y.-G. Kim, H.-S. Lim, and J.-W. Oh Protein Kinase C-related Kinase 2 Regulates Hepatitis C Virus RNA Polymerase Function by Phosphorylation J. Biol. Chem., November 26, 2004; 279(48): 50031 - 50041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Ferrari, R. Rossi, D. Arosio, A. Vindigni, G. Biamonti, and A. Montecucco Cell Cycle-dependent Phosphorylation of Human DNA Ligase I at the Cyclin-dependent Kinase Sites J. Biol. Chem., September 26, 2003; 278(39): 37761 - 37767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Salles-Passador, A. Munshi, D. Cannella, V. Pennaneach, S. Koundrioukoff, M. Jaquinod, E. Forest, V. Podust, A. Fotedar, and R. Fotedar Phosphorylation of the PCNA binding domain of the large subunit of replication factor C on Thr506 by cyclin-dependent kinases regulates binding to PCNA Nucleic Acids Res., September 1, 2003; 31(17): 5202 - 5211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Ott, C. Rehfuess, V. N. Podust, J. E. Clark, and E. Fanning Role of the p68 Subunit of Human DNA Polymerase {alpha}-Primase in Simian Virus 40 DNA Replication Mol. Cell. Biol., August 15, 2002; 22(16): 5669 - 5678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. K. Lobenhofer, L. Bennett, P. L. Cable, L. Li, P. R. Bushel, and C. A. Afshari Regulation of DNA Replication Fork Genes by 17{beta}-Estradiol Mol. Endocrinol., June 1, 2002; 16(6): 1215 - 1229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. P. Smith, C. Steffen, F. Grosse, and H.-P. Nasheuer Species Specificity of Simian Virus 40 DNA Replication in Vitro Requires Multiple Functions of Human DNA Polymerase alpha J. Biol. Chem., May 31, 2002; 277(23): 20541 - 20548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Melle and H.-P. Nasheuer Physical and functional interactions of the tumor suppressor protein p53 and DNA polymerase {alpha}-primase Nucleic Acids Res., April 1, 2002; 30(7): 1493 - 1499. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
