scholarly journals Lagging Strand DNA Synthesis at the Eukaryotic Replication Fork Involves Binding and Stimulation of FEN-1 by Proliferating Cell Nuclear Antigen

1995 ◽  
Vol 270 (38) ◽  
pp. 22109-22112 ◽  
Author(s):  
Xiangyang Li ◽  
Jun Li ◽  
John Harrington ◽  
Michael R. Lieber ◽  
Peter M. J. Burgers
Keyword(s):  
Dna Synthesis ◽  
Proliferating Cell Nuclear Antigen ◽  
Replication Fork ◽  
Nuclear Antigen ◽  
Proliferating Cell ◽  
Lagging Strand ◽  
Stimulation Of

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.

Different functional domains of the adenovirus E1A gene are involved in regulation of host cell cycle products

1987 ◽  
Vol 7 (2) ◽  
pp. 821-829
Author(s):  
B Zerler ◽  
R J Roberts ◽  
M B Mathews ◽  
E Moran
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Deletion Mutants ◽  
Terminal Exon ◽  
Adenovirus E1a ◽  
E1a Gene ◽  
Proliferating Cell ◽  
Stimulation Of

We have analyzed the cell cycle effects that different domains of the adenovirus E1A proteins have on quiescent primary BRK cells. Studies with deletion mutants that in combination removed all but the N-terminal 85 amino acids common to both the 12S and 13S proteins suggest that this region may be sufficient for the induction of synthesis of proliferating cell nuclear antigen and the stimulation of DNA synthesis. A second domain also common to the N-terminal exon of the 12S and 13S proteins was required for the induction of mitosis and stimulation of proliferation of primary BRK cells. A virus containing a mutation in this region was still able to stimulate DNA synthesis efficiently. A third domain, unique to the 13S protein, was required for the accelerated activation of the cellular thymidylate synthase gene in a manner similar to the 13S-dependent stimulation of adenovirus early region genes.

scholarly journals Different functional domains of the adenovirus E1A gene are involved in regulation of host cell cycle products.

1987 ◽  
Vol 7 (2) ◽  
pp. 821-829 ◽  
Author(s):  
B Zerler ◽  
R J Roberts ◽  
M B Mathews ◽  
E Moran
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Deletion Mutants ◽  
Terminal Exon ◽  
Adenovirus E1a ◽  
E1a Gene ◽  
Proliferating Cell ◽  
Stimulation Of

We have analyzed the cell cycle effects that different domains of the adenovirus E1A proteins have on quiescent primary BRK cells. Studies with deletion mutants that in combination removed all but the N-terminal 85 amino acids common to both the 12S and 13S proteins suggest that this region may be sufficient for the induction of synthesis of proliferating cell nuclear antigen and the stimulation of DNA synthesis. A second domain also common to the N-terminal exon of the 12S and 13S proteins was required for the induction of mitosis and stimulation of proliferation of primary BRK cells. A virus containing a mutation in this region was still able to stimulate DNA synthesis efficiently. A third domain, unique to the 13S protein, was required for the accelerated activation of the cellular thymidylate synthase gene in a manner similar to the 13S-dependent stimulation of adenovirus early region genes.

Demonstration of cell cycle kinetics in thyroid primary culture by immunostaining of proliferating cell nuclear antigen: differences in cyclic AMP-dependent and -independent mitogenic stimulations

1993 ◽  
Vol 105 (1) ◽  
pp. 69-80 ◽  
Author(s):  
M. Baptist ◽  
J.E. Dumont ◽  
P.P. Roger
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Primary Culture ◽  
Proliferating Cell Nuclear Antigen ◽  
Cell Cycle Progression ◽  
Nuclear Antigen ◽  
Major Influence ◽  
Cell Cycle Kinetics ◽  
Experimental Conditions ◽  
Proliferating Cell

In this study, experimental conditions are described that allowed us to follow the fate of the DNA polymerase delta-associated proliferating cell nuclear antigen (PCNA), by immunolabeling during the overall cell cycle. Differences in subcellular localization or the presence of PCNA allowed us to identify each phase of the cell cycle. Using these cell cycle markers in dog thyroid epithelial cells in primary culture, we found unexpected differences in cell cycle kinetics, in response to stimulations through cAMP-dependent and cAMP-independent pathways. These provide a new dimension to the view that the two pathways are largely separate, but co-operate on DNA synthesis initiation. More precisely, thyrotropin (TSH), acting via cAMP, exerts a potent triggering effect on DNA synthesis, associated with a precocious induction of PCNA appearance. This constitutes the major influence of TSH (cAMP) in determining cell cycle progression, which is only partly moderated by TSH-dependent lengthening of S- and G2-phases.

Dual mode of interaction of DNA polymerase ϵ with proliferating cell nuclear antigen in primer binding and DNA synthesis 1 1Edited by J. Karn

1999 ◽  
Vol 285 (1) ◽  
pp. 259-267 ◽  
Author(s):  
Giovanni Maga ◽  
Zophonı́as O Jónsson ◽  
Manuel Stucki ◽  
Silvio Spadari ◽  
Ulrich Hübscher
Keyword(s):  
Dna Synthesis ◽  
Dna Polymerase ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Dual Mode ◽  
Proliferating Cell

scholarly journals Structure of the processive human Pol δ holoenzyme

2019 ◽  
Author(s):  
Claudia Lancey ◽  
Muhammad Tehseen ◽  
Vlad-Stefan Raducanu ◽  
Fahad Rashid ◽  
Nekane Merino ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Structural Basis ◽  
Catalytic Core ◽  
Regulatory Subunits ◽  
Functional Interactions ◽  
Proliferating Cell ◽  
Lagging Strand ◽  
Catalytic Cleft

In eukaryotes, DNA polymerase δ (Pol δ) bound to the proliferating cell nuclear antigen (PCNA) replicates the lagging strand and cooperates with flap endonuclease 1 (FEN1) to process the Okazaki fragments for their ligation. We present the high-resolution cryo-EM structure of the human processive Pol δ-DNA-PCNA complex in the absence and presence of FEN1. Pol δ is anchored to one of the three PCNA monomers through the C-terminal domain of the catalytic subunit. The catalytic core sits on top of PCNA in an open configuration while the regulatory subunits project laterally. This arrangement allows PCNA to thread and stabilize the DNA exiting the catalytic cleft and recruit FEN1 to one unoccupied monomer in a toolbelt fashion. Alternative holoenzyme conformations reveal important functional interactions that maintain PCNA orientation during synthesis. This work sheds light on the structural basis of Pol δ’s activity in replicating the human genome.

scholarly journals The Effect of DNA Replication Mutations on CAG Tract Stability in Yeast

Genetics ◽  
1999 ◽  
Vol 152 (3) ◽  
pp. 953-963 ◽  
Author(s):  
Jill Kuglin Schweitzer ◽  
Dennis M Livingston
Keyword(s):  
Dna Replication ◽  
Proliferating Cell Nuclear Antigen ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Nuclear Antigen ◽  
Temperature Sensitive ◽  
Simple Repeats ◽  
Proliferating Cell ◽  
Lagging Strand ◽  
Palindromic Sequences

AbstractCAG repeat tracts are unstable in yeast, leading to frequent contractions and infrequent expansions in repeat tract length. To compare CAG repeats to other simple repeats and palindromic sequences, we examined the effect of DNA replication mutations, including alleles of pol α, pol δ, pol ϵ, and PCNA (proliferating cell nuclear antigen), on tract stability. Among the polymerase mutations, the pol δ mutation (pol3-14) destabilizes tracts with either CAG or CTG as the lagging strand template. One pol α mutation, pol1-1, destabilizes the orientation with CAG as the lagging strand template, but it has little effect on the CTG orientation. In contrast, the pol1-17 mutation has no effect on either orientation. Similarly, mutations in the proofreading functions of pol δ and pol ϵ, as well as a temperature-sensitive pol ϵ mutation, pol2-18, have no effect on tract stability. Three PCNA mutations, pol30-52, pol30-79, and pol30-90, all have drastic effects on tract stability. Of the three, pol30-52 is unique in yielding small tract changes that are indicative of an impairment in mismatch repair. These results show that while CAG repeats are destabilized by many of the same mutations that destabilize other simple repeats, they also have some behaviors that are suggestive of their potential to form hairpin structures.

Sign in / Sign up

Export Citation Format

Share Document