scholarly journals 3D Genome Organization: Causes and Consequences for DNA Damage and Repair

Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 7
Author(s):  
Ànnia Carré-Simon ◽  
Emmanuelle Fabre
Keyword(s):  
Dna Damage ◽  
Repair Process ◽  
Dna Damage And Repair ◽  
Strand Breaks ◽  
3D Genome ◽  
Cellular Processes ◽  
Genome Wide ◽  
Complex Landscape ◽  
Specific Stage ◽  
In Cis

The inability to repair damaged DNA severely compromises the integrity of any organism. In eukaryotes, the DNA damage response (DDR) operates within chromatin, a tightly organized DNA–histone complex in a non-random manner within the nucleus. Chromatin thus orchestrates various cellular processes, including repair. Here, we examine the chromatin landscape before, during, and after the DNA damage, focusing on double strand breaks (DSBs). We study how chromatin is modified during the repair process, not only around the damaged region (in cis), but also genome-wide (in trans). Recent evidence has highlighted a complex landscape in which different chromatin parameters (stiffness, compaction, loops) are transiently modified, defining “codes” for each specific stage of the DDR. We illustrate a novel aspect of DDR where chromatin modifications contribute to the movement of DSB-damaged chromatin, as well as undamaged chromatin, ensuring the mobilization of DSBs, their clustering, and their repair processes. 

scholarly journals Arsenic Biotransformation as a Cancer Promoting Factor by Inducing DNA Damage and Disruption of Repair Mechanisms

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Victor D. Martinez ◽  
Emily A. Vucic ◽  
Marta Adonis ◽  
Lionel Gil ◽  
Wan L. Lam
Keyword(s):  
Dna Damage ◽  
Drinking Water ◽  
Repair Process ◽  
Dna Methyltransferases ◽  
Health Concern ◽  
Dna Damage And Repair ◽  
Repair Mechanisms ◽  
Contaminated Drinking Water ◽  
High Concentrations ◽  
Epigenetic Patterns

Chronic exposure to arsenic in drinking water poses a major global health concern. Populations exposed to high concentrations of arsenic-contaminated drinking water suffer serious health consequences, including alarming cancer incidence and death rates. Arsenic is biotransformed through sequential addition of methyl groups, acquired from s-adenosylmethionine (SAM). Metabolism of arsenic generates a variety of genotoxic and cytotoxic species, damaging DNA directly and indirectly, through the generation of reactive oxidative species and induction of DNA adducts, strand breaks and cross links, and inhibition of the DNA repair process itself. Since SAM is the methyl group donor used by DNA methyltransferases to maintain normal epigenetic patterns in all human cells, arsenic is also postulated to affect maintenance of normal DNA methylation patterns, chromatin structure, and genomic stability. The biological processes underlying the cancer promoting factors of arsenic metabolism, related to DNA damage and repair, will be discussed here.

scholarly journals Virus DNA Replication and the Host DNA Damage Response

2018 ◽  
Vol 5 (1) ◽  
pp. 141-164 ◽  
Author(s):  
Matthew D. Weitzman ◽  
Amélie Fradet-Turcotte
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Life Cycles ◽  
Dynamic Interactions ◽  
Dna Damage And Repair ◽  
Dna Viruses ◽  
Cellular Processes ◽  
Damage Response ◽  
Cellular Replication ◽  
Cellular Dna

Viral DNA genomes have limited coding capacity and therefore harness cellular factors to facilitate replication of their genomes and generate progeny virions. Studies of viruses and how they interact with cellular processes have historically provided seminal insights into basic biology and disease mechanisms. The replicative life cycles of many DNA viruses have been shown to engage components of the host DNA damage and repair machinery. Viruses have evolved numerous strategies to navigate the cellular DNA damage response. By hijacking and manipulating cellular replication and repair processes, DNA viruses can selectively harness or abrogate distinct components of the cellular machinery to complete their life cycles. Here, we highlight consequences for viral replication and host genome integrity during the dynamic interactions between virus and host.

scholarly journals A CRISPR-based assay for the study of eukaryotic DNA repair onboard the International Space Station

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253403
Author(s):  
Sarah Stahl-Rommel ◽  
David Li ◽  
Michelle Sung ◽  
Rebecca Li ◽  
Aarthi Vijayakumar ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
International Space Station ◽  
Space Station ◽  
Repair Process ◽  
Double Strand Breaks ◽  
Repair Pathway ◽  
Strand Breaks ◽  
International Space ◽  
Break Site

As we explore beyond Earth, astronauts may be at risk for harmful DNA damage caused by ionizing radiation. Double-strand breaks are a type of DNA damage that can be repaired by two major cellular pathways: non-homologous end joining, during which insertions or deletions may be added at the break site, and homologous recombination, in which the DNA sequence often remains unchanged. Previous work suggests that space conditions may impact the choice of DNA repair pathway, potentially compounding the risks of increased radiation exposure during space travel. However, our understanding of this problem has been limited by technical and safety concerns, which have prevented integral study of the DNA repair process in space. The CRISPR/Cas9 gene editing system offers a model for the safe and targeted generation of double-strand breaks in eukaryotes. Here we describe a CRISPR-based assay for DNA break induction and assessment of double-strand break repair pathway choice entirely in space. As necessary steps in this process, we describe the first successful genetic transformation and CRISPR/Cas9 genome editing in space. These milestones represent a significant expansion of the molecular biology toolkit onboard the International Space Station.

scholarly journals Identification of Fungi Resistant to 137Cs Gamma Radiation From an Artwork by Candido Portinari

2021 ◽  
Author(s):  
Renata Cardoso ◽  
Fernanda Correa ◽  
Ana Chaves ◽  
Marcia Lutterbach ◽  
Ana Ferreira ◽  
...  
Keyword(s):  
Dna Damage ◽  
Gamma Radiation ◽  
High Efficiency ◽  
Art Collections ◽  
Dna Damage And Repair ◽  
Strand Breaks ◽  
Identification Of Fungi ◽  
Cesium 137 ◽  
Favorable Conditions ◽  
Ionizing Radiation Resistance

Abstract Gamma radiation is a safe and effective technique for the treatment of art collections being used with high efficiency in reducing microbial loads being obtained by the emission of a radioactive isotope, such as Cesium 137. Portinari's work, from the collection of the National Museum (Brazil), was analyzed and the fungi contained therein were collected, isolated, and further treated with gamma radiation for decontamination. Radiation doses used were 16, 19 and 22 kGy. Results indicated 11 genera and 17 species isolated. Penicillium and Cladosporium were isolated in air, artwork and its support - emphasizing the predominance they assume in the contamination of works of art under favorable conditions, such as museums. The genera Penicillium, Cladosporium, Nigrospora and Curvularia showed high resistances (16 kGy). The most resistant was Cladosporium, which showed no growth under 22 kGy. As there are some differences in ionizing radiation resistance among fungi from the same order or species, the results here outlined indicates that the rates of DNA damage and repair were critical, depending on chronic or acute dose irradiated. The biochemical mechanism acting on fungal cells under irradiation was basically the inactivation of specific enzymes and, probably, DNA damage, particularly stimulating double-strand breaks.

scholarly journals Comparison of Different Methods to Determine the DNA Sequence Preference of Ionising Radiation-Induced DNA Damage

Genes ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 8 ◽  
Author(s):  
Vincent Murray ◽  
Megan E. Hardie ◽  
Shweta D. Gautam
Keyword(s):  
Dna Damage ◽  
Dna Sequence ◽  
Consensus Sequence ◽  
Ionising Radiation ◽  
Next Generation ◽  
Linear Amplification ◽  
Strand Breaks ◽  
Sequence Preference ◽  
Genome Wide ◽  
Labelling Procedure

Ionising radiation (IR) is known to induce a wide variety of lesions in DNA. In this review, we compared three different techniques that examined the DNA sequence preference of IR-induced DNA damage at nucleotide resolution. These three techniques were: the linear amplification/polymerase stop assay, the end-labelling procedure, and Illumina next-generation genome-wide sequencing. The DNA sequence preference of IR-induced DNA damage was compared in purified DNA sequences including human genomic DNA. It was found that the DNA sequence preference of IR-induced DNA damage identified by the end-labelling procedure (that mainly detected single-strand breaks) and Illumina next-generation genome-wide sequencing (that mainly detected double-strand breaks) was at C nucleotides, while the linear amplification/polymerase stop assay (that mainly detected base damage) was at G nucleotides. A consensus sequence at the IR-induced DNA damage was found to be 5′-AGGC*C for the end-labelling technique, 5′-GGC*MH (where * is the cleavage site, M is A or C, H is any nucleotide except G) for the genome-wide technique, and 5′-GG* for the linear amplification/polymerase stop procedure. These three different approaches are important because they provide a deeper insight into the mechanism of action of IR-induced DNA damage.

scholarly journals Poly(ADP-ribosyl)ation mediates early phase histone eviction at DNA lesions

2020 ◽  
Vol 48 (6) ◽  
pp. 3001-3013 ◽  
Author(s):  
Guang Yang ◽  
Yibin Chen ◽  
Jiaxue Wu ◽  
Shih-Hsun Chen ◽  
Xiuhua Liu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Molecular Mechanism ◽  
Parp Inhibitor ◽  
Repair Process ◽  
Dna Lesions ◽  
Histone Chaperones ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Dna Lesion ◽  
Damage Repair

Abstract Nucleosomal histones are barriers to the DNA repair process particularly at DNA double-strand breaks (DSBs). However, the molecular mechanism by which these histone barriers are removed from the sites of DNA damage remains elusive. Here, we have generated a single specific inducible DSB in the cells and systematically examined the histone removal process at the DNA lesion. We found that histone removal occurred immediately following DNA damage and could extend up to a range of few kilobases from the lesion. To examine the molecular mechanism underlying DNA damage-induced histone removal, we screened histone modifications and found that histone ADP-ribosylation was associated with histone removal at DNA lesions. PARP inhibitor treatment suppressed the immediate histone eviction at DNA lesions. Moreover, we examined histone chaperones and found that the FACT complex recognized ADP-ribosylated histones and mediated the removal of histones in response to DNA damage. Taken together, our results reveal a pathway that regulates early histone barrier removal at DNA lesions. It may also explain the mechanism by which PARP inhibitor regulates early DNA damage repair.

scholarly journals Nanoformulation and Cancer Therapy: Study of DNA Damage and repair Pathway by Expression and Genome Wide Location Analysis (GWLA)

2007 ◽  
Vol 21 (6) ◽  
Author(s):  
Jean‐Bosco Tagne ◽  
Srikanth Kakumanu ◽  
Sumeet Gupta ◽  
Thomas Volkert ◽  
Richard Young ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cancer Therapy ◽  
Location Analysis ◽  
Repair Pathway ◽  
Dna Damage And Repair ◽  
Genome Wide
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