scholarly journals The Reactions of H2O2 and GSNO with the Zinc Finger Motif of XPA. Not A Regulatory Mechanism, But No Synergy with Cadmium Toxicity

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4177 ◽  
Author(s):  
Aleksandra Witkiewicz-Kucharczyk ◽  
Wojciech Goch ◽  
Jacek Olędzki ◽  
Andrea Hartwig ◽  
Wojciech Bal

Tetrathiolate zinc fingers are potential targets of oxidative assault under cellular stress conditions. We used the synthetic 37-residue peptide representing the tetrathiolate zinc finger domain of the DNA repair protein XPA, acetyl-DYVICEECGKEFMSYLMNHFDLPTCDNCRDADDKHK-amide (XPAzf) as a working model to study the reaction of its Zn(II) complex (ZnXPAzf) with hydrogen peroxide and S-nitrosoglutathione (GSNO), as oxidative and nitrosative stress agents, respectively. We also used the Cd(II) substituted XPAzf (CdXPAzf) to assess the situation of cadmium assault, which is accompanied by oxidative stress. Using electrospray mass spectrometry (ESI-MS), HPLC, and UV-vis and circular dichroism spectroscopies we demonstrated that even very low levels of H2O2 and GSNO invariably cause irreversible thiol oxidation and concomitant Zn(II) release from ZnXPAzf. In contrast, CdXPAzf was more resistant to oxidation, demonstrating the absence of synergy between cadmium and oxidative stresses. Our results indicate that GSNO cannot act as a reversible modifier of XPA, and rather has a deleterious effect on DNA repair.

2003 ◽  
Vol 16 (2) ◽  
pp. 242-248 ◽  
Author(s):  
Wojciech Bal ◽  
Tanja Schwerdtle ◽  
Andrea Hartwig

2005 ◽  
Vol 37 (9) ◽  
pp. 958-963 ◽  
Author(s):  
Amom Ruhikanta Meetei ◽  
Annette L Medhurst ◽  
Chen Ling ◽  
Yutong Xue ◽  
Thiyam Ramsing Singh ◽  
...  

2016 ◽  
Vol 55 (8) ◽  
pp. 2911-2915 ◽  
Author(s):  
Chao Wang ◽  
Daniel Abegg ◽  
Dominic G. Hoch ◽  
Alexander Adibekian

1995 ◽  
Vol 337 (1) ◽  
pp. 25-39 ◽  
Author(s):  
A.J. van Vuuren ◽  
E. Appeldoorn ◽  
H. Odijk ◽  
S. Humbert ◽  
V. Moncollin ◽  
...  

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Dhia Azzouz ◽  
Meraj A. Khan ◽  
Nades Palaniyar

AbstractReactive oxygen species (ROS) are essential for neutrophil extracellular trap (NET) formation or NETosis. Nevertheless, how ROS induces NETosis is unknown. Neutrophil activation induces excess ROS production and a meaningless genome-wide transcription to facilitate chromatin decondensation. Here we show that the induction of NADPH oxidase-dependent NETosis leads to extensive DNA damage, and the subsequent translocation of proliferating cell nuclear antigen (PCNA), a key DNA repair protein, stored in the cytoplasm into the nucleus. During the activation of NETosis (e.g., by phorbol myristate acetate, Escherichia coli LPS, Staphylococcus aureus (RN4220), or Pseudomonas aeruginosa), preventing the DNA-repair-complex assembly leading to nick formation that decondenses chromatin causes the suppression of NETosis (e.g., by inhibitors to, or knockdown of, Apurinic endonuclease APE1, poly ADP ribose polymerase PARP, and DNA ligase). The remaining repair steps involving polymerase activity and PCNA interactions with DNA polymerases β/δ do not suppress agonist-induced NETosis. Therefore, excess ROS produced during neutrophil activation induces NETosis by inducing extensive DNA damage (e.g., oxidising guanine to 8-oxoguanine), and the subsequent DNA repair pathway, leading to chromatin decondensation.


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