scholarly journals The Proliferating Cell Nuclear Antigen (PCNA)-interacting Protein (PIP) Motif of DNA Polymerase η Mediates Its Interaction with the C-terminal Domain of Rev1

2016 ◽  
Vol 291 (16) ◽  
pp. 8735-8744 ◽  
Author(s):  
Elizabeth M. Boehm ◽  
Kyle T. Powers ◽  
Christine M. Kondratick ◽  
Maria Spies ◽  
Jon C. D. Houtman ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Interacting Protein ◽  
Terminal Domain ◽  
Proliferating Cell

scholarly journals Identification of PCNA interacting protein motifs in human DNA polymerase delta

2020 ◽  
Author(s):  
Prashant Khandagale ◽  
Shweta Thakur ◽  
Narottam Acharya
Keyword(s):  
Dna Polymerase ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Dna Polymerase Delta ◽  
Interacting Protein ◽  
Protein Motifs ◽  
Human Dna ◽  
Biochemical Studies ◽  
Processivity Factor ◽  
Proliferating Cell

AbstractDNA polymerase delta (Polδ) is a highly processive essential replicative DNA polymerase. In humans, Polδ holoenzyme consists of p125, p50, p68, and p12 subunits and recently, we have shown that p12 exists as a dimer. Extensive biochemical studies suggest that all the subunits of Polδ interact with the processivity factor proliferating cell nuclear antigen (PCNA) to carry out a pivotal role in genomic DNA replication. While PCNA interaction protein (PIP) motifs in p68, p50 and p12 have been mapped, the PIP in p125, the catalytic subunit of the holoenzyme, remains elusive. Therefore, in this study by using multiple approaches we have conclusively mapped a non-canonical PIP box from residues 999VGGLLAFA1008 in p125, which binds to inter domain-connecting loop of PCNA with high affinity. Collectively, including previous studies, we conclude that similar to S. cerevisiae Polδ, each of the human Polδ subunits possess motif to interact with PCNA and significantly contribute towards the processive nature of this replicative DNA polymerase.

scholarly journals Identification of PCNA-interacting protein motifs in human DNA polymerase δ

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Prashant Khandagale ◽  
Shweta Thakur ◽  
Narottam Acharya
Keyword(s):  
Dna Polymerase ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Protein Motif ◽  
Interacting Protein ◽  
Protein Motifs ◽  
Dna Polymerase Δ ◽  
Human Dna ◽  
Processivity Factor ◽  
Proliferating Cell

Abstract DNA polymerase δ (Polδ) is a highly processive essential replicative DNA polymerase. In humans, the Polδ holoenzyme consists of p125, p50, p68 and p12 subunits and recently, we showed that the p12 subunit exists as a dimer. Extensive biochemical studies suggest that all the subunits of Polδ interact with the processivity factor proliferating cell nuclear antigen (PCNA) to carry out a pivotal role in genomic DNA replication. While PCNA-interacting protein motif (PIP) motifs in p68, p50 and p12 have been mapped, same in p125, the catalytic subunit of the holoenzyme, remains elusive. Therefore, in the present study by using multiple approaches we have conclusively mapped a non-canonical PIP motif from residues 999VGGLLAFA1008 in p125, which binds to the inter-domain-connecting loop (IDCL) of PCNA with high affinity. Collectively, including previous studies, we conclude that similar to Saccharomyces cerevisiae Polδ, each of the human Polδ subunits possesses motif to interact with PCNA and significantly contributes toward the processive nature of this replicative DNA polymerase.

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

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.

scholarly journals TRIM28 functions as the SUMO E3 ligase for PCNA in prevention of transcription induced DNA breaks

2020 ◽  
Vol 117 (38) ◽  
pp. 23588-23596
Author(s):  
Min Li ◽  
Xiaohua Xu ◽  
Chou-Wei Chang ◽  
Yilun Liu
Keyword(s):  
Rna Polymerase Ii ◽  
Proliferating Cell Nuclear Antigen ◽  
E3 Ligase ◽  
Nuclear Antigen ◽  
Dna Breaks ◽  
Interacting Protein ◽  
Proteomic Approach ◽  
Sumo E3 Ligase ◽  
Proliferating Cell

In human cells, the DNA replication factor proliferating cell nuclear antigen (PCNA) can be conjugated to either the small ubiquitinlike modifier SUMO1 or SUMO2, but only SUMO2-conjugated PCNA is induced by transcription to facilitate resolution of transcription–replication conflict (TRC). To date, the SUMO E3 ligase that provides substrate specificity for SUMO2-PCNA conjugation in response to TRC remains unknown. Using a proteomic approach, we identified TRIM28 as the E3 ligase that catalyzes SUMO2-PCNA conjugation. In vitro, TRIM28, together with the RNA polymerase II (RNAPII)-interacting protein RECQ5, promotes SUMO2-PCNA conjugation but inhibits SUMO1-PCNA formation. This activity requires a PCNA-interacting protein (PIP) motif located within the bromodomain of TRIM28. In cells, TRIM28 interaction with PCNA on human chromatin is dependent on both transcription and RECQ5, and SUMO2-PCNA level correlates with TRIM28 expression. As a consequence, TRIM28 depletion led to RNAPII accumulation at TRC sites, and expression of a TRIM28 PIP mutant failed to suppress TRC-induced DNA breaks.

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