scholarly journals The Friedreich's ataxia protein frataxin modulates DNA base excision repair in prokaryotes and mammals

2010 ◽  
Vol 432 (1) ◽  
pp. 165-172 ◽  
Author(s):  
René Thierbach ◽  
Gunnar Drewes ◽  
Markus Fusser ◽  
Anja Voigt ◽  
Doreen Kuhlow ◽  
...  
Keyword(s):  
Dna Repair ◽  
Neurodegenerative Disorder ◽  
Excision Repair ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Liver Tumours ◽  
Dna Repair Mechanisms ◽  
Dna Base ◽  
Repair Mechanisms ◽  
Base Excision

DNA-repair mechanisms enable cells to maintain their genetic information by protecting it from mutations that may cause malignant growth. Recent evidence suggests that specific DNA-repair enzymes contain ISCs (iron–sulfur clusters). The nuclearencoded protein frataxin is essential for the mitochondrial biosynthesis of ISCs. Frataxin deficiency causes a neurodegenerative disorder named Friedreich's ataxia in humans. Various types of cancer occurring at young age are associated with this disease, and hence with frataxin deficiency. Mice carrying a hepatocyte-specific disruption of the frataxin gene develop multiple liver tumours for unresolved reasons. In the present study, we show that frataxin deficiency in murine liver is associated with increased basal levels of oxidative DNA base damage. Accordingly, eukaryotic V79 fibroblasts overexpressing human frataxin show decreased basal levels of these modifications, while prokaryotic Salmonella enterica serotype Typhimurium TA104 strains transformed with human frataxin show decreased mutation rates. The repair rates of oxidative DNA base modifications in V79 cells overexpressing frataxin were significantly higher than in control cells. Lastly, cleavage activity related to the ISC-independent repair enzyme 8-oxoguanine glycosylase was found to be unaltered by frataxin overexpression. These findings indicate that frataxin modulates DNA-repair mechanisms probably due to its impact on ISC-dependent repair proteins, linking mitochondrial dysfunction to DNA repair and tumour initiation.

scholarly journals DNA repair-related genes in sugarcane expressed sequence tags (ESTs)

2001 ◽  
Vol 24 (1-4) ◽  
pp. 131-140 ◽  
Author(s):  
R.M.A. Costa ◽  
W.C. Lima ◽  
C.I.G. Vogel ◽  
C.M. Berra ◽  
D.D. Luche ◽  
...  
Keyword(s):  
Dna Repair ◽  
Expressed Sequence Tag ◽  
Excision Repair ◽  
Origin And Evolution ◽  
Dna Repair Mechanisms ◽  
Dna Lesion ◽  
Repair Mechanisms ◽  
Base Excision ◽  
High Level ◽  
Expressed Sequence

There is much interest in the identification and characterization of genes involved in DNA repair because of their importance in the maintenance of the genome integrity. The high level of conservation of DNA repair genes means that these genetic elements may be used in phylogenetic studies as a source of information on the genetic origin and evolution of species. The mechanisms by which damaged DNA is repaired are well understood in bacteria, yeast and mammals, but much remains to be learned as regards plants. We identified genes involved in DNA repair mechanisms in sugarcane using a similarity search of the Brazilian Sugarcane Expressed Sequence Tag (SUCEST) database against known sequences deposited in other public databases (National Center of Biotechnology Information (NCBI) database and the Munich Information Center for Protein Sequences (MIPS) Arabidopsis thaliana database). This search revealed that most of the various proteins involved in DNA repair in sugarcane are similar to those found in other eukaryotes. However, we also identified certain intriguing features found only in plants, probably due to the independent evolution of this kingdom. The DNA repair mechanisms investigated include photoreactivation, base excision repair, nucleotide excision repair, mismatch repair, non-homologous end joining, homologous recombination repair and DNA lesion tolerance. We report the main differences found in the DNA repair machinery in plant cells as compared to other organisms. These differences point to potentially different strategies plants employ to deal with DNA damage, that deserve further investigation.

scholarly journals Molecular Mechanisms of the Whole DNA Repair System: A Comparison of Bacterial and Eukaryotic Systems

2010 ◽  
Vol 2010 ◽  
pp. 1-32 ◽  
Author(s):  
Rihito Morita ◽  
Shuhei Nakane ◽  
Atsuhiro Shimada ◽  
Masao Inoue ◽  
Hitoshi Iino ◽  
...  
Keyword(s):  
Dna Repair ◽  
Molecular Mechanisms ◽  
Excision Repair ◽  
Thermus Thermophilus ◽  
Repair System ◽  
System A ◽  
Recombination Repair ◽  
Repair Mechanisms ◽  
Repair Pathways ◽  
Base Excision

DNA is subjected to many endogenous and exogenous damages. All organisms have developed a complex network of DNA repair mechanisms. A variety of different DNA repair pathways have been reported: direct reversal, base excision repair, nucleotide excision repair, mismatch repair, and recombination repair pathways. Recent studies of the fundamental mechanisms for DNA repair processes have revealed a complexity beyond that initially expected, with inter- and intrapathway complementation as well as functional interactions between proteins involved in repair pathways. In this paper we give a broad overview of the whole DNA repair system and focus on the molecular basis of the repair machineries, particularly inThermus thermophilusHB8.

scholarly journals Databases and Bioinformatics Tools for the Study of DNA Repair

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Kaja Milanowska ◽  
Kristian Rother ◽  
Janusz M. Bujnicki
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Excision Repair ◽  
Uv Light ◽  
Dna Lesions ◽  
Environmental Chemicals ◽  
Nonhomologous End Joining ◽  
End Joining ◽  
Repair Mechanisms ◽  
Base Excision

DNA is continuously exposed to many different damaging agents such as environmental chemicals, UV light, ionizing radiation, and reactive cellular metabolites. DNA lesions can result in different phenotypical consequences ranging from a number of diseases, including cancer, to cellular malfunction, cell death, or aging. To counteract the deleterious effects of DNA damage, cells have developed various repair systems, including biochemical pathways responsible for the removal of single-strand lesions such as base excision repair (BER) and nucleotide excision repair (NER) or specialized polymerases temporarily taking over lesion-arrested DNA polymerases during the S phase in translesion synthesis (TLS). There are also other mechanisms of DNA repair such as homologous recombination repair (HRR), nonhomologous end-joining repair (NHEJ), or DNA damage response system (DDR). This paper reviews bioinformatics resources specialized in disseminating information about DNA repair pathways, proteins involved in repair mechanisms, damaging agents, and DNA lesions.

scholarly journals PARP1 and PARP2 stabilise replication forks at base excision repair intermediates through Fbh1-dependent Rad51 regulation

2018 ◽  
Author(s):  
George E. Ronson ◽  
Ann Liza Piberger ◽  
Martin R. Higgs ◽  
Anna L. Olsen ◽  
Grant S. Stewart ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Damage Tolerance ◽  
Excision Repair ◽  
Replication Forks ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Dna Base ◽  
Repair Mechanisms ◽  
Base Excision

AbstractPARP1 regulates the repair of DNA single strand breaks (SSBs) generated directly, or during base excision repair (BER). However, the role of PARP2 in these and other repair mechanisms is unknown. Here, we report a requirement for PARP2 in stabilising replication forks that encounter BER intermediates through Fbh1-dependent regulation of Rad51. Whilst PARP2 is dispensable for tolerance of cells to SSBs or homologous recombination dysfunction, it is redundant with PARP1 in BER. Therefore, combined disruption of PARP1 and PARP2 leads to defective BER, resulting in elevated levels of replication associated DNA damage due to an inability to stabilise Rad51 at damaged replication forks and prevent uncontrolled DNA resection. Together, our results demonstrate how PARP1 and PARP2 regulate two independent, but intrinsically linked aspects of DNA base damage tolerance by promoting BER directly, and through stabilising replication forks that encounter BER intermediates.

scholarly journals RADIATION GENETICS IN MICROORGANISMS AND EVOLUTIONARY CONSIDERATIONS

Genetics ◽  
1974 ◽  
Vol 78 (1) ◽  
pp. 149-161
Author(s):  
Sohei Kondo
Keyword(s):  
Dna Repair ◽  
Molecular Mechanisms ◽  
Excision Repair ◽  
Resistance Mechanisms ◽  
Plant Viruses ◽  
Protective Capacity ◽  
E Coli ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms ◽  
Solar Uv

ABSTRACT Recent knowledge of UV-resistance mechanisms in microorganisms is reviewed in perspective, with emphasis on E. coli. Dark-repair genes are classified into "excision" and "tolerance" (ability to produce a normal copy of DNA from damaged DNA). The phenotype of DNA repair is rather common among the microorganisms compared, and yet their molecular mechanisms are not universal. In contrast, DNA photoreactivation is the simplest and the most general among these three repair systems. It is proposed that DNA repair mechanisms evolved in the order: photoreactivation, excision repair, and tolerance repair. The UV protective capacity and light-inducible RNA photoreactivation possessed by some plant viruses are interpreted to be the result of solar UV selection during a rather recent era of evolution.

scholarly journals The Effect of Allopregnanolone on Enzymatic Activity of the DNA Base Excision Repair Pathway in the Sheep Hippocampus and Amygdala under Natural and Stressful Conditions

2020 ◽  
Vol 21 (20) ◽  
pp. 7762
Author(s):  
Tomasz Misztal ◽  
Paweł Kowalczyk ◽  
Patrycja Młotkowska ◽  
Elżbieta Marciniak
Keyword(s):  
Dna Repair ◽  
Enzymatic Activity ◽  
Mrna Expression ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Dna Glycosylase ◽  
Repair Capacity ◽  
Dna Base Excision Repair ◽  
Dna Base ◽  
Base Excision

The neurosteroid allopregnanolone (AL) has many beneficial functions in the brain. This study tested the hypothesis that AL administered for three days into the third brain ventricle would affect the enzymatic activity of the DNA base excision repair (BER) pathway in the hippocampal CA1 and CA3 fields and the central amygdala in luteal-phase sheep under both natural and stressful conditions. Acute stressful stimuli, including isolation and partial movement restriction, were used on the last day of infusion. The results showed that stressful stimuli increased N-methylpurine DNA glycosylase (MPG), thymine DNA glycosylase (TDG), 8-oxoguanine glycosylase (OGG1), and AP-endonuclease 1 (APE1) mRNA expression, as well as repair activities for 1,N6-ethenoadenine (εA), 3,N4-ethenocytosine (εC), and 8-oxoguanine (8-oxoG) compared to controls. The stimulated events were lower in stressed and AL-treated sheep compared to sheep that were only stressed (except MPG mRNA expression in the CA1 and amygdala, as well as TDG mRNA expression in the CA1). AL alone reduced mRNA expression of all DNA repair enzymes (except TDG in the amygdala) relative to controls and other groups. DNA repair activities varied depending on the tissue—AL alone stimulated the excision of εA in the amygdala, εC in the CA3 and amygdala, and 8-oxoG in all tissues studied compared to controls. However, the excision efficiency of lesioned bases in the AL group was lower than in the stressed and stressed and AL-treated groups, with the exception of εA in the amygdala. In conclusion, the presented modulating effect of AL on the synthesis of BER pathway enzymes and their repair capacity, both under natural and stressful conditions, indicates another functional role of this neurosteroid in brain structures.

A DNA-repair pathway can affect transcriptional noise to promote cell fate transitions

Science ◽  
2021 ◽  
pp. eabc6506
Author(s):  
Ravi V. Desai ◽  
Xinyue Chen ◽  
Benjamin Martin ◽  
Sonali Chaturvedi ◽  
Dong Woo Hwang ◽  
...  
Keyword(s):  
Dna Repair ◽  
Cell Fate ◽  
Excision Repair ◽  
Dna Supercoiling ◽  
Cellular Reprogramming ◽  
Transcriptional Noise ◽  
Expression Noise ◽  
Dna Base ◽  
Base Modifications ◽  
Base Excision

Stochastic fluctuations in gene expression (‘noise’) are often considered detrimental, but fluctuations can also be exploited for benefit (e.g., dither). We show here that DNA base-excision repair amplifies transcriptional noise to facilitate cellular reprogramming. Specifically, the DNA-repair protein Apex1, which recognizes both naturally occurring and unnatural base modifications, amplifies expression noise while homeostatically maintaining mean-expression levels. This amplified expression noise originates from shorter duration, higher intensity, transcriptional bursts generated by Apex1-mediated DNA supercoiling. The remodeling of DNA topology first impedes and then accelerates transcription to maintain mean levels. This mechanism, which we term Discordant Transcription through Repair (DiThR; pronounced /’dither’/), potentiates cellular reprogramming and differentiation. Our study reveals a potential functional role for transcriptional fluctuations mediated by DNA base modifications in embryonic development and disease.

scholarly journals Plant homologue of human excision repair geneERCC1points to conservation of DNA repair mechanisms

1998 ◽  
Vol 13 (6) ◽  
pp. 823-829 ◽  
Author(s):  
Huiling Xu ◽  
Ines Swoboda ◽  
Prem L. Bhalla ◽  
Anneke M. Sijbers ◽  
Chongxin Zhao ◽  
...  
Keyword(s):  
Dna Repair ◽  
Excision Repair ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms ◽  
Plant Homologue

scholarly journals Nanoparticle-Encapsulated Camptothecin: Epigenetic Modulation in DNA Repair Mechanisms in Colon Cancer Cells

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5414
Author(s):  
Aisha Farhana ◽  
Avin Ee-Hwan Koh ◽  
Jia Bei Tong ◽  
Abdullah Alsrhani ◽  
Suresh Kumar Subbiah ◽  
...  
Keyword(s):  
Dna Repair ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Excision Repair ◽  
Cycle Arrest ◽  
Ht29 Cells ◽  
Regulatory Circuits ◽  
Repair Mechanisms ◽  
Base Excision ◽  
Epigenetic Modulation

Molecular crosstalk between the cellular epigenome and genome converge as a synergistic driver of oncogenic transformations. Besides other pathways, epigenetic regulatory circuits exert their effect towards cancer progression through the induction of DNA repair deficiencies. We explored this mechanism using a camptothecin encapsulated in β-cyclodextrin–EDTA–Fe3O4 nanoparticles (CPT-CEF)-treated HT29 cells model. We previously demonstrated that CPT-CEF treatment of HT29 cells effectively induces apoptosis and cell cycle arrest, stalling cancer progression. A comparative transcriptome analysis of CPT-CEF-treated versus untreated HT29 cells indicated that genes controlling mismatch repair, base excision repair, and homologues recombination were downregulated in these cancer cells. Our study demonstrated that treatment with CPT-CEF alleviated this repression. We observed that CPT-CEF exerts its effect by possibly affecting the DNA repair mechanism through epigenetic modulation involving genes of HMGB1, APEX1, and POLE3. Hence, we propose that CPT-CEF could be a DNA repair modulator that harnesses the cell’s epigenomic plasticity to amend DNA repair deficiencies in cancer cells.

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