scholarly journals A cell permeable bimane-constrained PCNA-interacting peptide

2021 ◽  
Author(s):  
Aimee Jade Horsfall ◽  
Beth A Vandborg ◽  
Zoya Kikhtyak ◽  
Denis Scanlon ◽  
Wayne D Tilley ◽  
...  
Keyword(s):  
Dna Replication ◽  
Therapeutic Target ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Sliding Clamp ◽  
Dna Replication And Repair ◽  
A Cell ◽  
Proliferating Cell

The human sliding clamp protein known as Proliferating Cell Nuclear Antigen (PCNA) orchestrates DNA-replication and -repair and as such is an ideal therapeutic target for proliferative diseases, including cancer. Peptides...

scholarly journals Maneuvers on PCNA Rings during DNA Replication and Repair

Genes ◽  
2018 ◽  
Vol 9 (8) ◽  
pp. 416 ◽  
Author(s):  
Dea Slade
Keyword(s):  
Dna Replication ◽  
Protein Interactions ◽  
Proliferating Cell Nuclear Antigen ◽  
Binding Proteins ◽  
Nuclear Antigen ◽  
Vast Number ◽  
Post Translational Modifications ◽  
Dna Replication And Repair ◽  
Replicative Polymerases ◽  
Proliferating Cell

DNA replication and repair are essential cellular processes that ensure genome duplication and safeguard the genome from deleterious mutations. Both processes utilize an abundance of enzymatic functions that need to be tightly regulated to ensure dynamic exchange of DNA replication and repair factors. Proliferating cell nuclear antigen (PCNA) is the major coordinator of faithful and processive replication and DNA repair at replication forks. Post-translational modifications of PCNA, ubiquitination and acetylation in particular, regulate the dynamics of PCNA-protein interactions. Proliferating cell nuclear antigen (PCNA) monoubiquitination elicits ‘polymerase switching’, whereby stalled replicative polymerase is replaced with a specialized polymerase, while PCNA acetylation may reduce the processivity of replicative polymerases to promote homologous recombination-dependent repair. While regulatory functions of PCNA ubiquitination and acetylation have been well established, the regulation of PCNA-binding proteins remains underexplored. Considering the vast number of PCNA-binding proteins, many of which have similar PCNA binding affinities, the question arises as to the regulation of the strength and sequence of their binding to PCNA. Here I provide an overview of post-translational modifications on both PCNA and PCNA-interacting proteins and discuss their relevance for the regulation of the dynamic processes of DNA replication and repair.

scholarly journals Human PCNA Structure, Function and Interactions

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 570 ◽  
Author(s):  
Amaia González-Magaña ◽  
Francisco J. Blanco
Keyword(s):  
Dna Replication ◽  
Structure Function ◽  
Binding Mode ◽  
Nuclear Antigen ◽  
Sequence Motif ◽  
Interacting Protein ◽  
Post Translational Modifications ◽  
Dna Replication And Repair ◽  
Dynamic Exchange ◽  
Proliferating Cell

Proliferating cell nuclear antigen (PCNA) is an essential factor in DNA replication and repair. It forms a homotrimeric ring that embraces the DNA and slides along it, anchoring DNA polymerases and other DNA editing enzymes. It also interacts with regulatory proteins through a sequence motif known as PCNA Interacting Protein box (PIP-box). We here review the latest contributions to knowledge regarding the structure-function relationships in human PCNA, particularly the mechanism of sliding, and of the molecular recognition of canonical and non-canonical PIP motifs. The unique binding mode of the oncogene p15 is described in detail, and the implications of the recently discovered structure of PCNA bound to polymerase δ are discussed. The study of the post-translational modifications of PCNA and its partners may yield therapeutic opportunities in cancer treatment, in addition to illuminating the way PCNA coordinates the dynamic exchange of its many partners in DNA replication and repair.

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 K6-linked SUMOylation of BAF regulates nuclear integrity and DNA replication in mammalian cells

2020 ◽  
Vol 117 (19) ◽  
pp. 10378-10387 ◽  
Author(s):  
Qiaoyu Lin ◽  
Bin Yu ◽  
Xiangyang Wang ◽  
Shicong Zhu ◽  
Gan Zhao ◽  
...  
Keyword(s):  
Dna Replication ◽  
Nuclear Localization ◽  
Proliferating Cell Nuclear Antigen ◽  
Mammalian Cells ◽  
Regulatory Mechanism ◽  
Nuclear Antigen ◽  
Multiple Functions ◽  
And Function ◽  
Proliferating Cell ◽  
Replication Failure

Barrier-to-autointegration factor (BAF) is a highly conserved protein in metazoans that has multiple functions during the cell cycle. We found that BAF is SUMOylated at K6, and that this modification is essential for its nuclear localization and function, including nuclear integrity maintenance and DNA replication. K6-linked SUMOylation of BAF promotes binding and interaction with lamin A/C to regulate nuclear integrity. K6-linked SUMOylation of BAF also supports BAF binding to DNA and proliferating cell nuclear antigen and regulates DNA replication. SENP1 and SENP2 catalyze the de-SUMOylation of BAF at K6. Disrupting the SUMOylation and de-SUMOylation cycle of BAF at K6 not only disturbs nuclear integrity, but also induces DNA replication failure. Taken together, our findings demonstrate that SUMOylation at K6 is an important regulatory mechanism that governs the nuclear functions of BAF in mammalian cells.

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.

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