Stimulation of DNA Polymerase γ Activity by Proliferating Cell Nuclear Antigen

1995 ◽  
Vol 216 (2) ◽  
pp. 715-722 ◽  
Author(s):  
T. Taguchi ◽  
M. Ogihara ◽  
T. Maekawa ◽  
F. Hanaoka ◽  
M. Tanno
Keyword(s):  
Dna Polymerase ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Proliferating Cell ◽  
Dna Polymerase Γ ◽  
Stimulation Of

scholarly journals Mutant DNA polymerase δ from thermosensitive Schizosaccharomyces pombe strains display reduced stimulation by proliferating cell nuclear antigen

1998 ◽  
Vol 335 (3) ◽  
pp. 581-588 ◽  
Author(s):  
Mylène PERDERISET ◽  
Giovanni MAGA ◽  
Karine PIARD ◽  
Stefania FRANCESCONI ◽  
Isabelle TRATNER ◽  
...  
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Dna Polymerase ◽  
Proliferating Cell Nuclear Antigen ◽  
Catalytic Subunit ◽  
Nuclear Antigen ◽  
Wild Type ◽  
Low Levels ◽  
Proliferating Cell ◽  
Stimulation Of

We have isolated and characterized DNA polymerase δ (pol δ) from two thermosensitive Schizosaccharomyces pombe strains, polδts1 and polδts3, mutated in two different evolutionarily conserved domains of the catalytic subunit. At the restrictive temperature of 37 °C polδts1 and polδts3 mutant strains arrest growth in the S phase of the cell cycle. We show that at low levels of primer ends, in vitro stimulation by proliferating cell nuclear antigen (PCNA) of mutant enzymes is lower than stimulation of wild-type pol δ. Affinity for primer (3´-OH) ends and processivity of mutant enzymes do not appear different from wild-type pol δ. In contrast, Vmax values are lower than the wild-type value. The major in vitro defect appears to be decreased stimulation of mutant enzymes by PCNA, resulting in reduced velocity of DNA synthesis. In addition, ts1 pol δ is not stimulated by low PCNA concentration at 37 °C, although low concentrations stimulate activity at 25 °C, suggesting that this thermolability at low levels of primer ends could be its critical defect in vivo. Thus, both ts1 and ts3 pol δ mutations are located in regions of the catalytic subunit that seem necessary, directly or indirectly, for its efficient interaction with PCNA.

Involvement of proliferating cell nuclear antigen (cyclin) in DNA replication in living cells

1989 ◽  
Vol 9 (1) ◽  
pp. 57-66
Author(s):  
M Zuber ◽  
E M Tan ◽  
M Ryoji
Keyword(s):  
Dna Polymerase ◽  
Proliferating Cell Nuclear Antigen ◽  
Living Cells ◽  
Nuclear Antigen ◽  
Plasmid Replication ◽  
Dna Polymerase Delta ◽  
Dna Polymerase Alpha ◽  
Proliferating Cell

Proliferating cell nuclear antigen (PCNA) (also called cyclin) is known to stimulate the activity of DNA polymerase delta but not the other DNA polymerases in vitro. We injected a human autoimmune antibody against PCNA into unfertilized eggs of Xenopus laevis and examined the effects of this antibody on the replication of injected plasmid DNA as well as egg chromosomes. The anti-PCNA antibody inhibited plasmid replication by up to 67%, demonstrating that PCNA is involved in plasmid replication in living cells. This result further implies that DNA polymerase delta is necessary for plasmid replication in vivo. Anti-PCNA antibody alone did not block plasmid replication completely, but the residual replication was abolished by coinjection of a monoclonal antibody against DNA polymerase alpha. Anti-DNA polymerase alpha alone inhibited plasmid replication by 63%. Thus, DNA polymerase alpha is also required for plasmid replication in this system. In similar studies on the replication of egg chromosomes, the inhibition by anti-PCNA antibody was only 30%, while anti-DNA polymerase alpha antibody blocked 73% of replication. We concluded that the replication machineries of chromosomes and plasmid differ in their relative content of DNA polymerase delta. In addition, we obtained evidence through the use of phenylbutyl deoxyguanosine, an inhibitor of DNA polymerase alpha, that the structure of DNA polymerase alpha holoenzyme for chromosome replication is significantly different from that for plasmid replication.

scholarly journals Oxidative DNA Damage Bypass in Arabidopsis thaliana Requires DNA Polymerase λ and Proliferating Cell Nuclear Antigen 2

2011 ◽  
Vol 23 (2) ◽  
pp. 806-822 ◽  
Author(s):  
Alessandra Amoroso ◽  
Lorenzo Concia ◽  
Caterina Maggio ◽  
Cécile Raynaud ◽  
Catherine Bergounioux ◽  
...  
Keyword(s):  
Dna Damage ◽  
Arabidopsis Thaliana ◽  
Dna Polymerase ◽  
Proliferating Cell Nuclear Antigen ◽  
Oxidative Dna Damage ◽  
Nuclear Antigen ◽  
Dna Polymerase Λ ◽  
Proliferating Cell

scholarly journals Stimulation of DNA synthesis by natural ceramide 1-phosphate

1997 ◽  
Vol 325 (2) ◽  
pp. 435-440 ◽  
Author(s):  
Antonio GOMEZ-MUÑOZ ◽  
Laura M. FRAGO ◽  
Luis ALVAREZ ◽  
Isabel VARELA-NIETO
Keyword(s):  
Dna Synthesis ◽  
Proliferating Cell Nuclear Antigen ◽  
Solvent Mixture ◽  
Mitogen Activated Protein Kinase ◽  
Nuclear Antigen ◽  
Tyrosine Residues ◽  
Mitogen Activated Protein ◽  
Ceramide 1 ◽  
Proliferating Cell ◽  
Stimulation Of

We found that natural (long-chain) ceramide 1-phosphate can be dispersed into aqueous solution when dissolved in an appropriate mixture of methanol/dodecane (49:1, v/v). This solvent mixture facilitates the interaction of this phosphosphingolipid with cells. Under these conditions, incubation of EGFR T17 fibroblasts with natural ceramide 1-phosphate caused a potent stimulation of DNA synthesis. This effect was accompanied by an increase in the levels of proliferating-cell nuclear antigen. Concentrations of natural ceramide 1-phosphate that stimulated the synthesis of DNA did not inhibit adenylate cyclase activity, nor did they stimulate phospholipase D. Natural ceramide 1-phosphate did not alter the cellular phosphorylation state of tyrosine residues or of mitogen-activated protein kinase. Furthermore, natural ceramide 1-phosphate failed to induce the expression of the proto-oncogenes c-myc and c-fos. Both the stimulation of DNA synthesis and the induction of proliferating-cell nuclear antigen by natural ceramide 1-phosphate were inhibited by natural ceramides. This work suggests that the use of methanol and dodecane to deliver natural ceramide 1-phosphate to cells may be useful for elucidation of the biological function(s) and mechanism(s) of action of ceramide 1-phosphate.

Fibroblast proliferation during myocardial development in rats is regulated by IGF-1 receptors

1995 ◽  
Vol 269 (3) ◽  
pp. H943-H951 ◽  
Author(s):  
K. Reiss ◽  
W. Cheng ◽  
J. Kajstura ◽  
E. H. Sonnenblick ◽  
L. G. Meggs ◽  
...  
Keyword(s):  
Dna Replication ◽  
Dna Polymerase ◽  
Proliferating Cell Nuclear Antigen ◽  
Cardiac Fibroblasts ◽  
Nuclear Antigen ◽  
Dna Polymerase Alpha ◽  
Myocardial Development ◽  
Left And Right ◽  
Proliferating Cell

To determine whether the growth of cardiac fibroblasts during development is modulated by the insulin-like growth factor (IGF)-1 receptor (IGF-1R), the expression of IGF-1, IGF-2, and IGF-1R was determined in fibroblasts from fetal and postnatal hearts. The expression of proliferating cell nuclear antigen (PCNA) and DNA polymerase-alpha was also evaluated in combination with the estimation of DNA replication. In comparison with fetal hearts, at postnatal day 21, fibroblast expression of IGF-1R mRNA, IGF-2, PCNA, and DNA polymerase-alpha was reduced by 77, 70, 80, and 86%, respectively. Moreover, IGF-1R protein decreased by 48% at 21 days. Bromodeoxyuridine labeling decreased by 88 and 89% in the left and right ventricle, respectively, at this time. Two different antisense oligodeoxynucleotides to IGF-1R reduced DNA replication by 60 and 44% in fibroblasts in culture. In addition, this intervention markedly attenuated the growth response of fibroblasts to IGF-1 or serum. In conclusion, the IGF-1R system appears to play a major role in the regulation of fibroblast growth in the heart in vivo.

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