Paulownia tomentosa (Princess Tree) Extract Reduces DNA Damage and Induces DNA Repair Processes in Skin Cells

AbstractMany mutagenic processes leave characteristic imprints on cancer genomes known as mutational signatures. These signatures have been of recent interest regarding their applicability in studying processes shaping the mutational landscape of cancer. In particular, pinpointing the presence of altered DNA repair pathways can have important therapeutic implications. However, mutational signatures of DNA repair deficiencies are often hard to infer. This challenge emerges as a result of deficient DNA repair processes acting by modifying the outcome of other mutagens. Thus, they exhibit non-additive effects that are not depicted by the current paradigm for modeling mutational processes as independent signatures. To close this gap, we present RepairSig, a method that accounts for interactions between DNA damage and repair and is able to uncover unbiased signatures of deficient DNA repair processes. In particular, RepairSig was able to replace three MMR deficiency signatures previously proposed to be active in breast cancer, with just one signature strikingly similar to the experimentally derived signature. As the first method to model interactions between mutagenic processes, RepairSig is an important step towards biologically more realistic modeling of mutational processes in cancer. The source code for RepairSig is publicly available at https://github.com/ncbi/RepairSig.

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An epigenetic code for DNA damage repair pathways?

Biochemistry and Cell Biology ◽

10.1139/o05-034 ◽

2005 ◽

Vol 83 (3) ◽

pp. 270-285 ◽

Cited By ~ 30

Author(s):

Paul O Hassa ◽

Michael O Hottiger

Keyword(s):

Dna Damage ◽

Dna Repair ◽

New Technologies ◽

Initial Step ◽

Genotoxic Stress ◽

Special Focus ◽

Nonhistone Proteins ◽

Repair Processes ◽

Epigenetic Code ◽

Repair Pathways

Exposure of living cells to intracellular or external mutagens results in DNA damage. Accumulation of DNA damage can lead to serious consequences because of the deleterious mutation rate resulting in genomic instability, cellular senescence, and cell death. To counteract genotoxic stress, cells have developed several strategies to detect defects in DNA structure. The eukaryotic genomic DNA is packaged through histone and nonhistone proteins into a highly condensed structure termed chromatin. Therefore the cellular enzymatic machineries responsible for DNA replication, recombination, and repair must circumvent this natural barrier in order to gain access to the DNA. Several studies have demonstrated that histone/chromatin modifications such as acetylation, methylation, and phosphorylation play crucial roles in DNA repair processes. This review will summarize the recent data that suggest a regulatory role of the epigenetic code in DNA repair processes. We will mainly focus on different covalent reversible modifications of histones as an initial step in early response to DNA damage and subsequent DNA repair. Special focus on a potential epigenetic histone code for these processes will be given in the last section. We also discuss new technologies and strategies to elucidate the putative epigenetic code for each of the DNA repair processes discussed.Key words: epigenetic code, histone modifications, DNA repair pathways, ChIP, MS/MS, acetylation, methylation, phosphorylation and mono(ADP-ribosyl)ation.

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DNA Repair Processes and Sensitivity to DNA Damage of Human Lymphocytes and Blasts: Analysis at the Single-Cell Level

Novel Approaches in Anticancer Drug Design - Contributions to Oncology ◽

10.1159/000424079 ◽

1995 ◽

pp. 155-161

Author(s):

Claudia Buschfort ◽

Frank Seiler ◽

Mark R. Müller ◽

Siegfried Seeber ◽

Manfred F. Rajewsky ◽

...

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Single Cell ◽

Human Lymphocytes ◽

Single Cell Level ◽

Cell Level ◽

Repair Processes

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Kinetic Modeling Reveals the Roles of Reactive Oxygen Species Scavenging and DNA Repair Processes in Shaping the Dose-Response Curve of KBrO3-Induced DNA Damage

Oxidative Medicine and Cellular Longevity ◽

10.1155/2015/764375 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

Maria A. Spassova ◽

David J. Miller ◽

Alexander S. Nikolov

Keyword(s):

Reactive Oxygen Species ◽

Dna Damage ◽

Dna Repair ◽

Base Excision Repair ◽

Dose Response ◽

Excision Repair ◽

Reactive Oxygen ◽

Oxygen Species ◽

Repair Processes ◽

Base Excision

We have developed a kinetic model to investigate how DNA repair processes and scavengers of reactive oxygen species (ROS) can affect the dose-response shape of prooxidant induced DNA damage. We used as an example chemicalKBrO3which is activated by glutathione and forms reactive intermediates that directly interact with DNA to form 8-hydroxy-2-deoxyguanosine DNA adducts (8-OH-dG). The single strand breaks (SSB) that can result from failed base excision repair of these adducts were considered as an effect downstream from 8-OH-dG. We previously demonstrated that, in the presence of effective base excision repair, 8-OH-dG can exhibit threshold-like dose-response dependence, while the downstream SSB can still exhibit a linear dose-response. Here we demonstrate that this result holds for a variety of conditions, including low levels of GSH, the presence of additional SSB repair mechanisms, or a scavenger. It has been shown that melatonin, a terminal scavenger, inhibitsKBrO3-caused oxidative damage. Our modeling revealed that sustained exposure toKBrO3can lead to fast scavenger exhaustion, in which case the dose-response shapes for both endpoints are not substantially affected. The results are important to consider when forming conclusions on a chemical’s toxicity dose dependence based on the dose-response of early genotoxic events.

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The Botanical Extract Feverfew PFE Reduces DNA Damage and Induces DNA Repair Processes

Selected Topics in DNA Repair ◽

10.5772/21216 ◽

2011 ◽

Author(s):

Michael D. ◽

Simarna Kaur ◽

Khalid Mahmoo

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Repair Processes ◽

Botanical Extract

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p53 mRNA Metabolism Links with the DNA Damage Response

Genes ◽

10.3390/genes12091446 ◽

2021 ◽

Vol 12 (9) ◽

pp. 1446

Author(s):

Sivakumar Vadivel Vadivel Gnanasundram ◽

Ondrej Bonczek ◽

Lixiao Wang ◽

Sa Chen ◽

Robin Fahraeus

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Dna Repair ◽

Dna Damage Response ◽

Rna Binding ◽

Rna Binding Proteins ◽

Genotoxic Stress ◽

Repair Processes ◽

Damage Response ◽

P53 Mrna

Human cells are subjected to continuous challenges by different genotoxic stress attacks. DNA damage leads to erroneous mutations, which can alter the function of oncogenes or tumor suppressors, resulting in cancer development. To circumvent this, cells activate the DNA damage response (DDR), which mainly involves cell cycle regulation and DNA repair processes. The tumor suppressor p53 plays a pivotal role in the DDR by halting the cell cycle and facilitating the DNA repair processes. Various pathways and factors participating in the detection and repair of DNA have been described, including scores of RNA-binding proteins (RBPs) and RNAs. It has become increasingly clear that p53’s role is multitasking, and p53 mRNA regulation plays a prominent part in the DDR. This review is aimed at covering the p53 RNA metabolism linked to the DDR and highlights the recent findings.

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