scholarly journals The Equally Important Role of Adenine Derivatives to That of Pyrimidine Derivatives in Near-0 eV Electron-Induced DNA Lesions

ChemPhysChem ◽  
2016 ◽  
Vol 17 (11) ◽  
pp. 1669-1677 ◽  
Author(s):  
Shoushan Wang ◽  
Peiwen Zhao ◽  
Changzhe Zhang ◽  
Yuxiang Bu
Keyword(s):  
Dna Lesions ◽  
Pyrimidine Derivatives ◽  
Adenine Derivatives

scholarly journals Theoretical Study on the Photo-Oxidation and Photoreduction of an Azetidine Derivative as a Model of DNA Repair

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2911
Author(s):  
Miriam Navarrete-Miguel ◽  
Antonio Francés-Monerris ◽  
Miguel A. Miranda ◽  
Virginie Lhiaubet-Vallet ◽  
Daniel Roca-Sanjuán
Keyword(s):  
Electron Transfer ◽  
Energy Barrier ◽  
Ring Opening ◽  
Dna Lesions ◽  
Barrier Heights ◽  
Dna Lesion ◽  
Electron Reduction ◽  
The Stability ◽  
Electron Transfer Processes

Photocycloreversion plays a central role in the study of the repair of DNA lesions, reverting them into the original pyrimidine nucleobases. Particularly, among the proposed mechanisms for the repair of DNA (6-4) photoproducts by photolyases, it has been suggested that it takes place through an intermediate characterized by a four-membered heterocyclic oxetane or azetidine ring, whose opening requires the reduction of the fused nucleobases. The specific role of this electron transfer step and its impact on the ring opening energetics remain to be understood. These processes are studied herein by means of quantum-chemical calculations on the two azetidine stereoisomers obtained from photocycloaddition between 6-azauracil and cyclohexene. First, we analyze the efficiency of the electron-transfer processes by computing the redox properties of the azetidine isomers as well as those of a series of aromatic photosensitizers acting as photoreductants and photo-oxidants. We find certain stereodifferentiation favoring oxidation of the cis-isomer, in agreement with previous experimental data. Second, we determine the reaction profiles of the ring-opening mechanism of the cationic, neutral, and anionic systems and assess their feasibility based on their energy barrier heights and the stability of the reactants and products. Results show that oxidation largely decreases the ring-opening energy barrier for both stereoisomers, even though the process is forecast as too slow to be competitive. Conversely, one-electron reduction dramatically facilitates the ring opening of the azetidine heterocycle. Considering the overall quantum-chemistry findings, N,N-dimethylaniline is proposed as an efficient photosensitizer to trigger the photoinduced cycloreversion of the DNA lesion model.

The Role of Platinum-DNA Lesions in the Inhibition of DNA Replication

1991 ◽  
pp. 181-193
Author(s):  
N. P. Johnson ◽  
J. L. Butour ◽  
C. Cayrol ◽  
S. Cros ◽  
M. Defais ◽  
...  
Keyword(s):  
Dna Replication ◽  
Dna Lesions

scholarly journals Cyclin Kinase-independent role of p21CDKN1A in the promotion of nascent DNA elongation in unstressed cells

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Sabrina F Mansilla ◽  
Agustina P Bertolin ◽  
Valérie Bergoglio ◽  
Marie-Jeanne Pillaire ◽  
Marina A González Besteiro ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Genomic Stability ◽  
S Phase ◽  
Fragile Sites ◽  
Dna Lesions ◽  
Cdk Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Independent Manner ◽  
Genomic Regions

The levels of the cyclin-dependent kinase (CDK) inhibitor p21 are low in S phase and insufficient to inhibit CDKs. We show here that endogenous p21, instead of being residual, it is functional and necessary to preserve the genomic stability of unstressed cells. p21depletion slows down nascent DNA elongation, triggers permanent replication defects and promotes the instability of hard-to-replicate genomic regions, namely common fragile sites (CFS). The p21’s PCNA interacting region (PIR), and not its CDK binding domain, is needed to prevent the replication defects and the genomic instability caused by p21 depletion. The alternative polymerase kappa is accountable for such defects as they were not observed after simultaneous depletion of both p21 and polymerase kappa. Hence, in CDK-independent manner, endogenous p21 prevents a type of genomic instability which is not triggered by endogenous DNA lesions but by a dysregulation in the DNA polymerase choice during genomic DNA synthesis.

scholarly journals Novel Role of mfd: Effects on Stationary-Phase Mutagenesis in Bacillus subtilis

2006 ◽  
Vol 188 (21) ◽  
pp. 7512-7520 ◽  
Author(s):  
Christian Ross ◽  
Christine Pybus ◽  
Mario Pedraza-Reyes ◽  
Huang-Mo Sung ◽  
Ronald E. Yasbin ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Rna Polymerase ◽  
Stationary Phase ◽  
Coupling Factor ◽  
Dna Lesions ◽  
Adaptive Mutagenesis ◽  
Associated Proteins ◽  
Mutagenic Process ◽  
Protein Transcription

ABSTRACT Previously, using a chromosomal reversion assay system, we established that an adaptive mutagenic process occurs in nongrowing Bacillus subtilis cells under stress, and we demonstrated that multiple mechanisms are involved in generating these mutations (41, 43). In an attempt to delineate how these mutations are generated, we began an investigation into whether or not transcription and transcription-associated proteins influence adaptive mutagenesis. In B. subtilis, the Mfd protein (transcription repair coupling factor) facilitates removal of RNA polymerase stalled at transcriptional blockages and recruitment of repair proteins to DNA lesions on the transcribed strand. Here we demonstrate that the loss of Mfd has a depressive effect on stationary-phase mutagenesis. An association between Mfd mutagenesis and aspects of transcription is discussed.

Platelet mitochondrial dysfunction and the correlation with human diseases

2017 ◽  
Vol 45 (6) ◽  
pp. 1213-1223 ◽  
Author(s):  
Li Wang ◽  
Qiang Wu ◽  
Zhijia Fan ◽  
Rufeng Xie ◽  
Zhicheng Wang ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disorders ◽  
Dna Lesions ◽  
Human Diseases ◽  
Mitochondrial Apoptosis ◽  
Electron Transfer Chain ◽  
Transfer Chain ◽  
And Oxidative Stress ◽  
Potential Biomarkers

The platelet is considered as an accessible and valuable tool to study mitochondrial function, owing to its greater content of fully functional mitochondria compared with other metabolically active organelles. Different lines of studies have demonstrated that mitochondria in platelets have function far more than thrombogenesis regulation, and beyond hemostasis, platelet mitochondrial dysfunction has also been used for studying mitochondrial-related diseases. In this review, the interplay between platelet mitochondrial dysfunction and oxidative stress, mitochondrial DNA lesions, electron transfer chain impairments, mitochondrial apoptosis and mitophagy has been outlined. Meanwhile, considerable efforts have been made towards understanding the role of platelet mitochondrial dysfunction in human diseases, such as diabetes mellitus, sepsis and neurodegenerative disorders. Alongside this, we have also articulated our perspectives on the development of potential biomarkers of platelet mitochondrial dysfunction in mitochondrial-related diseases.

scholarly journals The role of Sp1 in the detection and elimination of cells with persistent DNA strand breaks

NAR Cancer ◽  
2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Polina S Loshchenova ◽  
Svetlana V Sergeeva ◽  
Sally C Fletcher ◽  
Grigory L Dianov
Keyword(s):  
Dna Damage ◽  
Cancer Therapy ◽  
Genome Stability ◽  
Dna Strand Breaks ◽  
Dna Lesions ◽  
Exogenous Dna ◽  
Strand Breaks ◽  
Specificity Factor ◽  
Dna Strand

Abstract Maintenance of genome stability suppresses cancer and other human diseases and is critical for organism survival. Inevitably, during a life span, multiple DNA lesions can arise due to the inherent instability of DNA molecules or due to endogenous or exogenous DNA damaging factors. To avoid malignant transformation of cells with damaged DNA, multiple mechanisms have evolved to repair DNA or to detect and eradicate cells accumulating unrepaired DNA damage. In this review, we discuss recent findings on the role of Sp1 (specificity factor 1) in the detection and elimination of cells accumulating persistent DNA strand breaks. We also discuss how this mechanism may contribute to the maintenance of physiological populations of healthy cells in an organism, thus preventing cancer formation, and the possible application of these findings in cancer therapy.

scholarly journals De novo phosphorylation of H2AX by WSTF regulates transcription-coupled homologous recombination repair

2019 ◽  
Vol 47 (12) ◽  
pp. 6299-6314 ◽  
Author(s):  
Jae-Hoon Ji ◽  
Sunwoo Min ◽  
Sunyoung Chae ◽  
Geun-Hyoung Ha ◽  
Yonghyeon Kim ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Rna Polymerase Ii ◽  
De Novo ◽  
Dna Lesions ◽  
Proliferating Cells ◽  
Histone H2ax ◽  
Rna Transcripts ◽  
Recombination Repair ◽  
Active Transcription

Abstract Histone H2AX undergoes a phosphorylation switch from pTyr142 (H2AX-pY142) to pSer139 (γH2AX) in the DNA damage response (DDR); however, the functional role of H2AX-pY142 remains elusive. Here, we report a new layer of regulation involving transcription-coupled H2AX-pY142 in the DDR. We found that constitutive H2AX-pY142 generated by Williams-Beuren syndrome transcription factor (WSTF) interacts with RNA polymerase II (RNAPII) and is associated with RNAPII-mediated active transcription in proliferating cells. Also, removal of pre-existing H2AX-pY142 by ATM-dependent EYA1/3 phosphatases disrupts this association and requires for transcriptional silencing at transcribed active damage sites. The following recovery of H2AX-pY142 via translocation of WSTF to DNA lesions facilitates transcription-coupled homologous recombination (TC-HR) in the G1 phase, whereby RAD51 loading, but not RPA32, utilizes RNAPII-dependent active RNA transcripts as donor templates. We propose that the WSTF-H2AX-RNAPII axis regulates transcription and TC-HR repair to maintain genome integrity.

scholarly journals Role of Double-Stranded DNA Translocase Activity of Human HLTF in Replication of Damaged DNA

2009 ◽  
Vol 30 (3) ◽  
pp. 684-693 ◽  
Author(s):  
András Blastyák ◽  
Ildikó Hajdú ◽  
Ildikó Unk ◽  
Lajos Haracska
Keyword(s):  
Translesion Synthesis ◽  
Dna Lesions ◽  
Template Switching ◽  
Replication Forks ◽  
Double Stranded Dna ◽  
Fork Regression ◽  
Dna Translocase ◽  
Damaged Dna

ABSTRACT Unrepaired DNA lesions can block the progression of the replication fork, leading to genomic instability and cancer in higher-order eukaryotes. In Saccharomyces cerevisiae, replication through DNA lesions can be mediated by translesion synthesis DNA polymerases, leading to error-free or error-prone damage bypass, or by Rad5-mediated template switching to the sister chromatid that is inherently error free. While translesion synthesis pathways are highly conserved from yeast to humans, very little is known of a Rad5-like pathway in human cells. Here we show that a human homologue of Rad5, HLTF, can facilitate fork regression and has a role in replication of damaged DNA. We found that HLTF is able to reverse model replication forks, a process which depends on its double-stranded DNA translocase activity. Furthermore, from analysis of isolated dually labeled chromosomal fibers, we demonstrate that in vivo, HLTF promotes the restart of replication forks blocked at DNA lesions. These findings suggest that HLTF can promote error-free replication of damaged DNA and support a role for HLTF in preventing mutagenesis and carcinogenesis, providing thereby for its potential tumor suppressor role.

The Role of Nucleobase Carboradical and Carbanion on DNA Lesions:  A Theoretical Study

2006 ◽  
Vol 110 (46) ◽  
pp. 23583-23589 ◽  
Author(s):  
Ru bo Zhang ◽  
Leif A. Eriksson
Keyword(s):  
Theoretical Study ◽  
Dna Lesions
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