scholarly journals Metal Ions Modify in Vitro DNA Damage Yields With High-LET Radiation

2021 ◽  
Author(s):  
Dylan Buglewicz ◽  
Cathy Su ◽  
Austin Banks ◽  
Jazmine Strenger-smith ◽  
Suad Elmegerhi ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Dna Damage ◽  
Strand Break ◽  
Single Strand ◽  
Iron Ion ◽  
Single Strand Break ◽  
Carbon Ion ◽  
X Ray ◽  
High Let ◽  
Break Formation

Abstract Cu2+ and Co2+ are metals known to increase DNA damage in the presence of hydrogen peroxide through a Fenton type reaction. We hypothesized that these metals could increase DNA damage following irradiations of increasing LET values as hydrogen peroxide is a product of the radiolysis of water. The reaction mixtures contain either double- or single-stranded DNA in solution with Cu2+ or Co2+ and was irradiated either with X-ray, carbon-ion or iron-ion beams or was treated with hydrogen peroxide or bleomycin at increasing radiation dosages or chemical concentrations. DNA damage was then assessed by gel electrophoresis followed by band intensity analysis. DNA in solution with metals demonstrated the most DNA damage when treated with hydrogen peroxide followed by irradiation with low-LET (X-Ray), high-LET (carbon-ion and iron-ion), respectively, and demonstrated the least damage with treatment of bleomycin. Cu2+ portrayed greater DNA damage than Co2+ following all experimental conditions. The metals effect caused more DNA damage and was observed to be LET dependent for single-strand break formation but inversely dependent for double-strand break formation. These results suggest that Cu2+ is more efficient than Co2+ at inducing both DNA single-strand and double-strand breaks following all irradiations and chemical treatments.

Effects of Singlet Oxygen on the Biological Activity of DNA and Its Involvement in Single Strand-Break Formation

1988 ◽  
pp. 473-477
Author(s):  
Heribert Wefers ◽  
Paolo Di Mascio ◽  
Hong-Phuc Do-Thi ◽  
Dietrich Schulte-Frohlinde ◽  
Helmut Sies
Keyword(s):  
Biological Activity ◽  
Singlet Oxygen ◽  
Strand Break ◽  
Single Strand ◽  
Single Strand Break ◽  
Break Formation

End-damage-specific proteins facilitate recruitment or stability of X-ray cross-complementing protein 1 at the sites of DNA single-strand break repair

FEBS Journal ◽  
2005 ◽  
Vol 272 (22) ◽  
pp. 5753-5763 ◽  
Author(s):  
Jason L. Parsons ◽  
Irina I. Dianova ◽  
Emma Boswell ◽  
Michael Weinfeld ◽  
Grigory L. Dianov
Keyword(s):  
Strand Break ◽  
Single Strand ◽  
Single Strand Break ◽  
X Ray ◽  
Single Strand Break Repair ◽  
Specific Proteins ◽  
Break Repair

scholarly journals Single-Strand Break End Resection in Genome Integrity: Mechanism and Regulation by APE2

2018 ◽  
Vol 19 (8) ◽  
pp. 2389 ◽  
Author(s):  
Md. Hossain ◽  
Yunfeng Lin ◽  
Shan Yan
Keyword(s):  
Dna Damage ◽  
Genome Instability ◽  
Strand Break ◽  
Single Strand ◽  
Genome Integrity ◽  
Single Strand Break ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Damage Response ◽  
End Resection

DNA single-strand breaks (SSBs) occur more than 10,000 times per mammalian cell each day, representing the most common type of DNA damage. Unrepaired SSBs compromise DNA replication and transcription programs, leading to genome instability. Unrepaired SSBs are associated with diseases such as cancer and neurodegenerative disorders. Although canonical SSB repair pathway is activated to repair most SSBs, it remains unclear whether and how unrepaired SSBs are sensed and signaled. In this review, we propose a new concept of SSB end resection for genome integrity. We propose a four-step mechanism of SSB end resection: SSB end sensing and processing, as well as initiation, continuation, and termination of SSB end resection. We also compare different mechanisms of SSB end resection and DSB end resection in DNA repair and DNA damage response (DDR) pathways. We further discuss how SSB end resection contributes to SSB signaling and repair. We focus on the mechanism and regulation by APE2 in SSB end resection in genome integrity. Finally, we identify areas of future study that may help us gain further mechanistic insight into the process of SSB end resection. Overall, this review provides the first comprehensive perspective on SSB end resection in genome integrity.

scholarly journals APE2 promotes DNA damage response pathway from a single-strand break

2018 ◽  
Vol 46 (5) ◽  
pp. 2479-2494 ◽  
Author(s):  
Yunfeng Lin ◽  
Liping Bai ◽  
Steven Cupello ◽  
Md Akram Hossain ◽  
Bradley Deem ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Strand Break ◽  
Single Strand ◽  
Single Strand Break ◽  
Damage Response ◽  
Dna Damage Response Pathway

scholarly journals APE2 Zf-GRF facilitates 3′-5′ resection of DNA damage following oxidative stress

2016 ◽  
Vol 114 (2) ◽  
pp. 304-309 ◽  
Author(s):  
Bret D. Wallace ◽  
Zachary Berman ◽  
Geoffrey A. Mueller ◽  
Yunfeng Lin ◽  
Timothy Chang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Nucleic Acid ◽  
Oxidative Dna Damage ◽  
Strand Break ◽  
Binding Activity ◽  
Nucleic Acid Binding ◽  
Catalytic Core ◽  
Single Strand Break ◽  
X Ray

The Xenopus laevis APE2 (apurinic/apyrimidinic endonuclease 2) nuclease participates in 3′-5′ nucleolytic resection of oxidative DNA damage and activation of the ATR-Chk1 DNA damage response (DDR) pathway via ill-defined mechanisms. Here we report that APE2 resection activity is regulated by DNA interactions in its Zf-GRF domain, a region sharing high homology with DDR proteins Topoisomerase 3α (TOP3α) and NEIL3 (Nei-like DNA glycosylase 3), as well as transcription and RNA regulatory proteins, such as TTF2 (transcription termination factor 2), TFIIS, and RPB9. Biochemical and NMR results establish the nucleic acid-binding activity of the Zf-GRF domain. Moreover, an APE2 Zf-GRF X-ray structure and small-angle X-ray scattering analyses show that the Zf-GRF fold is typified by a crescent-shaped ssDNA binding claw that is flexibly appended to an APE2 endonuclease/exonuclease/phosphatase (EEP) catalytic core. Structure-guided Zf-GRF mutations impact APE2 DNA binding and 3′-5′ exonuclease processing, and also prevent efficient APE2-dependent RPA recruitment to damaged chromatin and activation of the ATR-Chk1 DDR pathway in response to oxidative stress in Xenopus egg extracts. Collectively, our data unveil the APE2 Zf-GRF domain as a nucleic acid interaction module in the regulation of a key single-strand break resection function of APE2, and also reveal topologic similarity of the Zf-GRF to the zinc ribbon domains of TFIIS and RPB9.

scholarly journals DNA single-strand break-induced DNA damage response causes heart failure

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Tomoaki Higo ◽  
Atsuhiko T. Naito ◽  
Tomokazu Sumida ◽  
Masato Shibamoto ◽  
Katsuki Okada ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Strand Break ◽  
Single Strand ◽  
Single Strand Break ◽  
Damage Response

scholarly journals Comparison of High- and Low-LET Radiation-Induced DNA Double-Strand Break Processing in Living Cells

2020 ◽  
Vol 21 (18) ◽  
pp. 6602 ◽  
Author(s):  
Stefan J. Roobol ◽  
Irene van den Bent ◽  
Wiggert A. van Cappellen ◽  
Tsion E. Abraham ◽  
Maarten W. Paul ◽  
...  
Keyword(s):  
Dna Damage ◽  
Protein A ◽  
Strand Break ◽  
Double Strand Break ◽  
Protein Accumulation ◽  
Dna Double Strand Breaks ◽  
X Ray ◽  
High Let ◽  
Dna End Resection ◽  
Α Particles

High-linear-energy-transfer (LET) radiation is more lethal than similar doses of low-LET radiation types, probably a result of the condensed energy deposition pattern of high-LET radiation. Here, we compare high-LET α-particle to low-LET X-ray irradiation and monitor double-strand break (DSB) processing. Live-cell microscopy was used to monitor DNA double-strand breaks (DSBs), marked by p53-binding protein 1 (53BP1). In addition, the accumulation of the endogenous 53BP1 and replication protein A (RPA) DSB processing proteins was analyzed by immunofluorescence. In contrast to α-particle-induced 53BP1 foci, X-ray-induced foci were resolved quickly and more dynamically as they showed an increase in 53BP1 protein accumulation and size. In addition, the number of individual 53BP1 and RPA foci was higher after X-ray irradiation, while focus intensity was higher after α-particle irradiation. Interestingly, 53BP1 foci induced by α-particles contained multiple RPA foci, suggesting multiple individual resection events, which was not observed after X-ray irradiation. We conclude that high-LET α-particles cause closely interspaced DSBs leading to high local concentrations of repair proteins. Our results point toward a change in DNA damage processing toward DNA end-resection and homologous recombination, possibly due to the depletion of soluble protein in the nucleoplasm. The combination of closely interspaced DSBs and perturbed DNA damage processing could be an explanation for the increased relative biological effectiveness (RBE) of high-LET α-particles compared to X-ray irradiation.

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