Drug–DNA complexation as the key factor in photosensitized thymine dimerization

2017 ◽  
Vol 19 (7) ◽  
pp. 4951-4955 ◽  
Author(s):  
M. Consuelo Cuquerella ◽  
Virginie Lhiaubet-Vallet ◽  
Miguel A. Miranda ◽  
Francisco Bosca
Keyword(s):  
Dna Damage ◽  
Crucial Role ◽  
Transient Absorption ◽  
Cyclobutane Pyrimidine Dimers ◽  
Absorption And Emission ◽  
Pyrimidine Dimers ◽  
Key Factor

The crucial role of photosensitizer@DNA complexation in the formation of cyclobutane pyrimidine dimers (CPDs) has been demonstrated using femtosecond and nanosecond transient absorption and emission measurements in combination with in vitro DNA damage assays.

scholarly journals A Role for Histone H2B During Repair of UV-Induced DNA Damage in Saccharomyces cerevisiae

Genetics ◽  
2002 ◽  
Vol 160 (4) ◽  
pp. 1375-1387
Author(s):  
Emmanuelle M D Martini ◽  
Scott Keeney ◽  
Mary Ann Osley
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Chromatin Structure ◽  
Specific Effect ◽  
Cell Killing ◽  
Cyclobutane Pyrimidine Dimers ◽  
Histone H2b ◽  
Uv Sensitivity ◽  
Pyrimidine Dimers

Abstract To investigate the role of the nucleosome during repair of DNA damage in yeast, we screened for histone H2B mutants that were sensitive to UV irradiation. We have isolated a new mutant, htb1-3, that shows preferential sensitivity to UV-C. There is no detectable difference in bulk chromatin structure or in the number of UV-induced cis-syn cyclobutane pyrimidine dimers (CPD) between HTB1 and htb1-3 strains. These results suggest a specific effect of this histone H2B mutation in UV-induced DNA repair processes rather than a global effect on chromatin structure. We analyzed the UV sensitivity of double mutants that contained the htb1-3 mutation and mutations in genes from each of the three epistasis groups of RAD genes. The htb1-3 mutation enhanced UV-induced cell killing in rad1Δ and rad52Δ mutants but not in rad6Δ or rad18Δ mutants, which are defective in postreplicational DNA repair (PRR). When combined with other mutations that affect PRR, the histone mutation increased the UV sensitivity of strains with defects in either the error-prone (rev1Δ) or error-free (rad30Δ) branches of PRR, but did not enhance the UV sensitivity of a strain with a rad5Δ mutation. When combined with a ubc13Δ mutation, which is also epistatic with rad5Δ, the htb1-3 mutation enhanced UV-induced cell killing. These results suggest that histone H2B acts in a novel RAD5-dependent branch of PRR.

scholarly journals LINC-PINT impedes DNA repair and enhances radiotherapeutic response by targeting DNA-PKcs in nasopharyngeal cancer

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
You-hong Wang ◽  
Zhen Guo ◽  
Liang An ◽  
Yong Zhou ◽  
Heng Xu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Nasopharyngeal Cancer ◽  
Noncoding Rnas ◽  
Dependent Protein Kinase ◽  
Damage Repair ◽  
Dependent Protein ◽  
Cancer Tissues

AbstractRadioresistance continues to be the leading cause of recurrence and metastasis in nasopharyngeal cancer. Long noncoding RNAs are emerging as regulators of DNA damage and radioresistance. LINC-PINT was originally identified as a tumor suppressor in various cancers. In this study, LINC-PINT was significantly downregulated in nasopharyngeal cancer tissues than in rhinitis tissues, and low LINC-PINT expressions showed poorer prognosis in patients who received radiotherapy. We further identified a functional role of LINC-PINT in inhibiting the malignant phenotypes and sensitizing cancer cells to irradiation in vitro and in vivo. Mechanistically, LINC-PINT was responsive to DNA damage, inhibiting DNA damage repair through ATM/ATR-Chk1/Chk2 signaling pathways. Moreover, LINC-PINT increased radiosensitivity by interacting with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and negatively regulated the expression and recruitment of DNA-PKcs. Therefore, these findings collectively support the possibility that LINC-PINT serves as an attractive target to overcome radioresistance in NPC.

scholarly journals Genotoxicity and inflammatory potential of stainless steel welding fume particles: an in vitro study on standard vs Cr(VI)-reduced flux-cored wires and the role of released metals

2021 ◽  
Author(s):  
Sarah McCarrick ◽  
Valentin Romanovski ◽  
Zheng Wei ◽  
Elin M. Westin ◽  
Kjell-Arne Persson ◽  
...  
Keyword(s):  
Dna Damage ◽  
In Vitro Study ◽  
Human Monocyte ◽  
Welding Fumes ◽  
Welding Fume ◽  
Increased Risk ◽  
Underlying Mechanisms ◽  
Cored Wires

AbstractWelders are daily exposed to various levels of welding fumes containing several metals. This exposure can lead to an increased risk for different health effects which serves as a driving force to develop new methods that generate less toxic fumes. The aim of this study was to explore the role of released metals for welding particle-induced toxicity and to test the hypothesis that a reduction of Cr(VI) in welding fumes results in less toxicity by comparing the welding fume particles of optimized Cr(VI)-reduced flux-cored wires (FCWs) to standard FCWs. The welding particles were thoroughly characterized, and toxicity (cell viability, DNA damage and inflammation) was assessed following exposure to welding particles as well as their released metal fraction using cultured human bronchial epithelial cells (HBEC-3kt, 5–100 µg/mL) and human monocyte-derived macrophages (THP-1, 10–50 µg/mL). The results showed that all Cr was released as Cr(VI) for welding particles generated using standard FCWs whereas only minor levels (< 3% of total Cr) were released from the newly developed FCWs. Furthermore, the new FCWs were considerably less cytotoxic and did not cause any DNA damage in the doses tested. For the standard FCWs, the Cr(VI) released in cell media seemed to explain a large part of the cytotoxicity and DNA damage. In contrast, all particles caused rather similar inflammatory effects suggesting different underlying mechanisms. Taken together, this study suggests a potential benefit of substituting standard FCWs with Cr(VI)-reduced wires to achieve less toxic welding fumes and thus reduced risks for welders.

Temperature-dependence of the DnaA–DNA interaction and its effect on the autoregulation of dnaA expression

2012 ◽  
Vol 449 (2) ◽  
pp. 333-341 ◽  
Author(s):  
Chiara Saggioro ◽  
Anne Olliver ◽  
Bianca Sclavi
Keyword(s):  
Temperature Dependence ◽  
Binding Sites ◽  
Dna Interaction ◽  
Bacterial Dna ◽  
Dnaa Protein ◽  
High Affinity ◽  
Key Factor

The DnaA protein is a key factor for the regulation of the timing and synchrony of initiation of bacterial DNA replication. The transcription of the dnaA gene in Escherichia coli is regulated by two promoters, dnaAP1 and dnaAP2. The region between these two promoters contains several DnaA-binding sites that have been shown to play an important role in the negative auto-regulation of dnaA expression. The results obtained in the present study using an in vitro and in vivo quantitative analysis of the effect of mutations to the high-affinity DnaA sites reveal an additional effect of positive autoregulation. We investigated the role of transcription autoregulation in the change of dnaA expression as a function of temperature. While negative auto-regulation is lost at dnaAP1, the effects of both positive and negative autoregulation are maintained at the dnaAP2 promoter upon lowering the growth temperature. These observations can be explained by the results obtained in vitro showing a difference in the temperature-dependence of DnaA–ATP binding to its high- and low-affinity sites, resulting in a decrease in DnaA–ATP oligomerization at lower temperatures. The results of the present study underline the importance of the role for autoregulation of gene expression in the cellular adaptation to different growth temperatures.

Role of oxygen derivatives in the cytotoxicity and DNA damage produced by asbestos on rat pleural mesothelial cells in vitro

1994 ◽  
Vol 15 (6) ◽  
pp. 1251-1255 ◽  
Author(s):  
Hang Ying Dong ◽  
Annie Buard ◽  
Annie Renier ◽  
Francoise Lévy ◽  
Laure Saint-Etienne ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mesothelial Cells ◽  
Pleural Mesothelial Cells

The External Relations of Tatarstan: In Pursuit of Sovereignty, or Playing the Sub-Nationalist Card?

2010 ◽  
Vol 5 (1-2) ◽  
pp. 99-124 ◽  
Author(s):  
Elena Albina
Keyword(s):  
Russian Federation ◽  
Crucial Role ◽  
Positive Outcome ◽  
Present Contribution ◽  
Regional Coordination ◽  
External Relations ◽  
Key Factor ◽  
Negative Effect ◽  
The Russian Federation

This article deliberates on the effects of sub-nationalism on the profile of a region in external relations. The questions under consideration in the present contribution are: (1) does nationalism make the external relations of a region conflictual vis-à-vis the federal centre?; and (2) to what extent can its alleged ill effect be counter-balanced by the well-elaborated mechanism of centre-regional coordination? This article aims to contest the assumptions of mainstream thinking in the literature on paradiplomacy, which suggests that sub-nationalism might have a negative effect and that strong institutions are indispensable for a positive outcome. Relying on an analysis of external relations in Tatarstan, a republic in the Russian Federation, this contribution illustrates the crucial role of the ‘manipulative’ form of nationalism as a key factor shaping the functional character of paradiplomacy.

scholarly journals γH2AX in the S Phase after UV Irradiation Corresponds to DNA Replication and Does Not Report on the Extent of DNA Damage

2020 ◽  
Vol 40 (20) ◽  
Author(s):  
Shivnarayan Dhuppar ◽  
Sitara Roy ◽  
Aprotim Mazumder
Keyword(s):  
Dna Damage ◽  
Uv Irradiation ◽  
S Phase ◽  
Dna Double Strand Breaks ◽  
Cyclobutane Pyrimidine Dimers ◽  
Environmental Mutagen ◽  
Strand Breaks ◽  
Pyrimidine Dimers ◽  
Replication Sites ◽  
A Cell

ABSTRACT Ultraviolet (UV) radiation is a major environmental mutagen. Exposure to UV leads to a sharp peak of γH2AX, the phosphorylated form of the histone variant H2AX, in the S phase within an asynchronous population of cells. γH2AX is often considered a definitive marker of DNA damage inside a cell. In this report, we show that γH2AX in the S-phase cells after UV irradiation reports neither on the extent of primary DNA damage in the form of cyclobutane pyrimidine dimers nor on the extent of its secondary manifestations in the form of DNA double-strand breaks or in the inhibition of global transcription. Instead, γH2AX in the S phase corresponds to the sites of active replication at the time of UV irradiation. This accumulation of γH2AX at replication sites slows down the replication. However, the cells do complete the replication of their genomes and arrest within the G2 phase. Our study suggests that it is not DNA damage, but the response elicited, which peaks in the S phase upon UV irradiation.

scholarly journals SIRT7-mediated ATM deacetylation is essential for its deactivation and DNA damage repair

2019 ◽  
Vol 5 (3) ◽  
pp. eaav1118 ◽  
Author(s):  
Ming Tang ◽  
Zhiming Li ◽  
Chaohua Zhang ◽  
Xiaopeng Lu ◽  
Bo Tu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Repair ◽  
Class Iii ◽  
Ataxia Telangiectasia Mutated ◽  
Damage Repair ◽  
Damage Response ◽  
Late Stages

The activation of ataxia-telangiectasia mutated (ATM) upon DNA damage involves a cascade of reactions, including acetylation by TIP60 and autophosphorylation. However, how ATM is progressively deactivated after completing DNA damage repair remains obscure. Here, we report that sirtuin 7 (SIRT7)–mediated deacetylation is essential for dephosphorylation and deactivation of ATM. We show that SIRT7, a class III histone deacetylase, interacts with and deacetylates ATM in vitro and in vivo. In response to DNA damage, SIRT7 is mobilized onto chromatin and deacetylates ATM during the late stages of DNA damage response, when ATM is being gradually deactivated. Deacetylation of ATM by SIRT7 is prerequisite for its dephosphorylation by its phosphatase WIP1. Consequently, depletion of SIRT7 or acetylation-mimic mutation of ATM induces persistent ATM phosphorylation and activation, thus leading to impaired DNA damage repair. Together, our findings reveal a previously unidentified role of SIRT7 in regulating ATM activity and DNA damage repair.

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