scholarly journals Control of PCNA deubiquitylation in yeast

2010 ◽  
Vol 38 (1) ◽  
pp. 104-109 ◽  
Author(s):  
Alfonso Gallego-Sánchez ◽  
Francisco Conde ◽  
Pedro San Segundo ◽  
Avelino Bueno
Keyword(s):  
Dna Damage ◽  
Crucial Role ◽  
Proliferating Cell Nuclear Antigen ◽  
Molecular Mechanisms ◽  
Damage Tolerance ◽  
Nuclear Antigen ◽  
Dna Damage Tolerance ◽  
Sliding Clamp ◽  
Evolutionarily Conserved ◽  
Proliferating Cell

Eukaryotes ubiquitylate the replication factor PCNA (proliferating-cell nuclear antigen) so that it tolerates DNA damage. Although, in the last few years, the understanding of the evolutionarily conserved mechanism of ubiquitylation of PCNA, and its crucial role in DNA damage tolerance, has progressed impressively, little is known about the deubiquitylation of this sliding clamp in most organisms. In the present review, we will discuss potential molecular mechanisms regulating PCNA deubiquitylation in yeast.

scholarly journals The ADP-ribosyltransferase PARP10/ARTD10 Interacts with Proliferating Cell Nuclear Antigen (PCNA) and Is Required for DNA Damage Tolerance

2014 ◽  
Vol 289 (19) ◽  
pp. 13627-13637 ◽  
Author(s):  
Claudia M. Nicolae ◽  
Erin R. Aho ◽  
Alexander H. S. Vlahos ◽  
Katherine N. Choe ◽  
Subhajyoti De ◽  
...  
Keyword(s):  
Dna Damage ◽  
Proliferating Cell Nuclear Antigen ◽  
Damage Tolerance ◽  
Nuclear Antigen ◽  
Dna Damage Tolerance ◽  
Adp Ribosyltransferase ◽  
Proliferating Cell

scholarly journals Monoubiquitination of Proliferating Cell Nuclear Antigen Induced by Stalled Replication Requires Uncoupling of DNA Polymerase and Mini-chromosome Maintenance Helicase Activities

2006 ◽  
Vol 281 (43) ◽  
pp. 32081-32088 ◽  
Author(s):  
Debbie J. Chang ◽  
Patrick J. Lupardus ◽  
Karlene A. Cimprich
Keyword(s):  
Dna Damage ◽  
Dna Polymerase ◽  
Proliferating Cell Nuclear Antigen ◽  
Molecular Mechanisms ◽  
Genotoxic Stress ◽  
Nuclear Antigen ◽  
Single Stranded Dna ◽  
Independent Events ◽  
Atr Activation ◽  
Proliferating Cell

Proliferating cell nuclear antigen (PCNA) is a homotrimeric, ring-shaped protein complex that functions as a processivity factor for DNA polymerases. Following genotoxic stress, PCNA is modified at a conserved site by either a single ubiquitin moiety or a polyubiquitin chain. These modifications are required to coordinate DNA damage tolerance processes with ongoing replication. The molecular mechanisms responsible for inducing PCNA ubiquitination are not well understood. Using Xenopus egg extracts, we show that ultraviolet radiation and aphidicolin treatment induce the mono- and diubiquitination of PCNA. PCNA ubiquitination is replication-dependent and coincides with activation of the ataxia telangiectasia mutated and Rad3-related (ATR)-dependent DNA damage checkpoint pathway. However, loss of ATR signaling by depletion of the ATR-interacting protein (ATRIP) or Rad1, a component of the 911 checkpoint clamp, does not impair PCNA ubiquitination. Primed single-stranded DNA generated by uncoupling of mini-chromosome maintenance helicase and DNA polymerase activities has been shown previously to be necessary for ATR activation. Here we show that PCNA ubiquitination also requires uncoupling of helicase and polymerase activities. We further demonstrate that replicating single-stranded DNA, which mimics the structure produced upon uncoupling, is sufficient to induce PCNA monoubiquitination. Our results suggest that PCNA ubiquitination and ATR activation are two independent events that occur in response to a common single-stranded DNA intermediate generated by functional uncoupling of mini-chromosome maintenance (MCM) helicase and DNA polymerase activities.

DNA-damage tolerance through PCNA ubiquitination and sumoylation

2020 ◽  
Vol 477 (14) ◽  
pp. 2655-2677
Author(s):  
Li Fan ◽  
Tonghui Bi ◽  
Linxiao Wang ◽  
Wei Xiao
Keyword(s):  
Dna Damage ◽  
Posttranslational Modifications ◽  
Damage Tolerance ◽  
Nuclear Antigen ◽  
Replication Forks ◽  
Dna Damage Tolerance ◽  
Yeast Saccharomyces Cerevisiae ◽  
Dna Damaging Agents ◽  
Template Switch ◽  
Proliferating Cell

DNA-damage tolerance (DDT) is employed by eukaryotic cells to bypass replication-blocking lesions induced by DNA-damaging agents. In budding yeast Saccharomyces cerevisiae, DDT is mediated by RAD6 epistatic group genes and the central event for DDT is sequential ubiquitination of proliferating cell nuclear antigen (PCNA), a DNA clamp required for replication and DNA repair. DDT consists of two parallel pathways: error-prone DDT is mediated by PCNA monoubiquitination, which recruits translesion synthesis DNA polymerases to bypass lesions with decreased fidelity; and error-free DDT is mediated by K63-linked polyubiquitination of PCNA at the same residue of monoubiquitination, which facilitates homologous recombination-mediated template switch. Interestingly, the same PCNA residue is also subjected to sumoylation, which leads to inhibition of unwanted recombination at replication forks. All three types of PCNA posttranslational modifications require dedicated conjugating and ligation enzymes, and these enzymes are highly conserved in eukaryotes, from yeast to human.

scholarly journals Helicase-Like Transcription Factor HLTF and E3 Ubiquitin Ligase SHPRH Confer DNA Damage Tolerance through Direct Interactions with Proliferating Cell Nuclear Antigen (PCNA)

2020 ◽  
Vol 21 (3) ◽  
pp. 693 ◽  
Author(s):  
Mareike Seelinger ◽  
Marit Otterlei
Keyword(s):  
Dna Damage ◽  
Transcription Factor ◽  
Damage Tolerance ◽  
Genome Instability ◽  
Ring Finger ◽  
Nuclear Antigen ◽  
Common Mutation ◽  
Dna Damage Tolerance ◽  
Replicative Stress ◽  
Template Switch

To prevent replication fork collapse and genome instability under replicative stress, DNA damage tolerance (DDT) mechanisms have evolved. The RAD5 homologs, HLTF (helicase-like transcription factor) and SHPRH (SNF2, histone-linker, PHD and RING finger domain-containing helicase), both ubiquitin ligases, are involved in several DDT mechanisms; DNA translesion synthesis (TLS), fork reversal/remodeling and template switch (TS). Here we show that these two human RAD5 homologs contain functional APIM PCNA interacting motifs. Our results show that both the role of HLTF in TLS in HLTF overexpressing cells, and nuclear localization of SHPRH, are dependent on interaction of HLTF and SHPRH with PCNA. Additionally, we detected multiple changes in the mutation spectra when APIM in overexpressed HLTF or SHPRH were mutated compared to overexpressed wild type proteins. In plasmids from cells overexpressing the APIM mutant version of HLTF, we observed a decrease in C to T transitions, the most common mutation caused by UV irradiation, and an increase in mutations on the transcribed strand. These results strongly suggest that direct binding of HLTF and SHPRH to PCNA is vital for their function in DDT.

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 Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival

2010 ◽  
Vol 207 (12) ◽  
pp. 2631-2645 ◽  
Author(s):  
Véronique Witko-Sarsat ◽  
Julie Mocek ◽  
Dikra Bouayad ◽  
Nicola Tamassia ◽  
Jean-Antoine Ribeil ◽  
...  
Keyword(s):  
Proliferating Cell Nuclear Antigen ◽  
Molecular Mechanisms ◽  
Kinase Inhibitor ◽  
Nuclear Antigen ◽  
Neutrophil Apoptosis ◽  
Proliferating Cells ◽  
Rna Transfection ◽  
Neutrophil Survival ◽  
Proliferating Cell

Neutrophil apoptosis is a highly regulated process essential for inflammation resolution, the molecular mechanisms of which are only partially elucidated. In this study, we describe a survival pathway controlled by proliferating cell nuclear antigen (PCNA), a nuclear factor involved in DNA replication and repairing of proliferating cells. We show that mature neutrophils, despite their inability to proliferate, express high levels of PCNA exclusively in their cytosol and constitutively associated with procaspases, presumably to prevent their activation. Notably, cytosolic PCNA abundance decreased during apoptosis, and increased during in vitro and in vivo exposure to the survival factor granulocyte colony-stimulating factor (G-CSF). Peptides derived from the cyclin-dependent kinase inhibitor p21, which compete with procaspases to bind PCNA, triggered neutrophil apoptosis thus demonstrating that specific modification of PCNA protein interactions affects neutrophil survival. Furthermore, PCNA overexpression rendered neutrophil-differentiated PLB985 myeloid cells significantly more resistant to TNF-related apoptosis-inducing ligand– or gliotoxin-induced apoptosis. Conversely, a decrease in PCNA expression after PCNA small interfering RNA transfection sensitized these cells to apoptosis. Finally, a mutation in the PCNA interdomain-connecting loop, the binding site for many partners, significantly decreased the PCNA-mediated antiapoptotic effect. These results identify PCNA as a regulator of neutrophil lifespan, thereby highlighting a novel target to potentially modulate pathological inflammation.

Proliferating cell nuclear antigen destabilizes c-Abl tyrosine kinase and regulates cell apoptosis in response to DNA damage

APOPTOSIS ◽  
2009 ◽  
Vol 14 (3) ◽  
pp. 268-275 ◽  
Author(s):  
Xiang He ◽  
Congwen Wei ◽  
Ting Song ◽  
Jing Yuan ◽  
Yanhong Zhang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Tyrosine Kinase ◽  
Cell Apoptosis ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Abl Tyrosine Kinase ◽  
Proliferating Cell

Interaction between proliferating cell nuclear antigen (PCNA) and a DnaJ induced by DNA damage

2005 ◽  
Vol 118 (2) ◽  
pp. 91-97 ◽  
Author(s):  
Taichi Yamamoto ◽  
Yoko Mori ◽  
Toyotaka Ishibashi ◽  
Yukinobu Uchiyama ◽  
Tadamasa Ueda ◽  
...  
Keyword(s):  
Dna Damage ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Proliferating Cell
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