scholarly journals Base Excision Repair Pathways

10.5772/22171 ◽  
2011 ◽  
Author(s):  
Christina Emmanouil
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Repair Pathways ◽  
Base Excision

Proteins of nucleotide and base excision repair pathways interact in mitochondria to protect from loss of subcutaneous fat, a hallmark of aging

2010 ◽  
Vol 188 (3) ◽  
pp. i3-i3
Author(s):  
York Kamenisch ◽  
Maria Fousteri ◽  
Jennifer Knoch ◽  
Anna-Katharina von Thaler ◽  
Birgit Fehrenbacher ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Subcutaneous Fat ◽  
Repair Pathways ◽  
Base Excision

scholarly journals Epistatic role of base excision repair and mismatch repair pathways in mediating cisplatin cytotoxicity

2013 ◽  
Vol 41 (15) ◽  
pp. 7332-7343 ◽  
Author(s):  
Anbarasi Kothandapani ◽  
Akshada Sawant ◽  
Venkata Srinivas Mohan Nimai Dangeti ◽  
Robert W. Sobol ◽  
Steve M. Patrick
Keyword(s):  
Mismatch Repair ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Repair Pathways ◽  
Base Excision

scholarly journals The involvement of nucleotide excision repair proteins in the removal of oxidative DNA damage

2020 ◽  
Vol 48 (20) ◽  
pp. 11227-11243 ◽  
Author(s):  
Namrata Kumar ◽  
Sripriya Raja ◽  
Bennett Van Houten
Keyword(s):  
Nucleotide Excision Repair ◽  
Base Excision Repair ◽  
Oxidative Dna Damage ◽  
Excision Repair ◽  
Base Damage ◽  
The Past ◽  
Nucleotide Excision ◽  
Oxidative Processes ◽  
Repair Pathways ◽  
Base Excision

Abstract The six major mammalian DNA repair pathways were discovered as independent processes, each dedicated to remove specific types of lesions, but the past two decades have brought into focus the significant interplay between these pathways. In particular, several studies have demonstrated that certain proteins of the nucleotide excision repair (NER) and base excision repair (BER) pathways work in a cooperative manner in the removal of oxidative lesions. This review focuses on recent data showing how the NER proteins, XPA, XPC, XPG, CSA, CSB and UV-DDB, work to stimulate known glycosylases involved in the removal of certain forms of base damage resulting from oxidative processes, and also discusses how some oxidative lesions are probably directly repaired through NER. Finally, since many glycosylases are inhibited from working on damage in the context of chromatin, we detail how we believe UV-DDB may be the first responder in altering the structure of damage containing-nucleosomes, allowing access to BER enzymes.

scholarly journals Contribution of Base Excision Repair, Nucleotide Excision Repair, and DNA Recombination to Alkylation Resistance of the Fission Yeast Schizosaccharomyces pombe

2000 ◽  
Vol 182 (8) ◽  
pp. 2104-2112 ◽  
Author(s):  
Asli Memisoglu ◽  
Leona Samson
Keyword(s):  
Dna Repair ◽  
Schizosaccharomyces Pombe ◽  
Nucleotide Excision Repair ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Dna Recombination ◽  
Nucleotide Excision ◽  
Repair Pathways ◽  
Base Excision

ABSTRACT DNA damage is unavoidable, and organisms across the evolutionary spectrum possess DNA repair pathways that are critical for cell viability and genomic stability. To understand the role of base excision repair (BER) in protecting eukaryotic cells against alkylating agents, we generated Schizosaccharomyces pombe strains mutant for the mag1 3-methyladenine DNA glycosylase gene. We report that S. pombe mag1 mutants have only a slightly increased sensitivity to methylation damage, suggesting that Mag1-initiated BER plays a surprisingly minor role in alkylation resistance in this organism. We go on to show that other DNA repair pathways play a larger role than BER in alkylation resistance. Mutations in genes involved in nucleotide excision repair (rad13) and recombinational repair (rhp51) are much more alkylation sensitive thanmag1 mutants. In addition, S. pombe mutant for the flap endonuclease rad2 gene, whose precise function in DNA repair is unclear, were also more alkylation sensitive thanmag1 mutants. Further, mag1 andrad13 interact synergistically for alkylation resistance, and mag1 and rhp51 display a surprisingly complex genetic interaction. A model for the role of BER in the generation of alkylation-induced DNA strand breaks in S. pombe is discussed.

Potentiation of Melphalan-Induced Cytotoxicity through Targeting of the Base Excision Repair Pathway in Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4799-4799
Author(s):  
April M. Reed ◽  
Melissa L. Fishel ◽  
Mark R. Kelley ◽  
Rafat Abonour
Keyword(s):  
Multiple Myeloma ◽  
Dna Damage ◽  
Dna Repair ◽  
Side Effects ◽  
Small Molecule ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Chemotherapeutic Agents ◽  
Repair Pathways ◽  
Base Excision

Abstract Melphalan (M) is an active agent against multiple myeloma (MM). One of the obstacles with M treatment is the patient’s ability to tolerate side effects such as mucositis and pancytopenia. This is especially true for those patients >70 years of age. We hypothesize that potentiation of M-induced cytotoxicity is possible in MM with agents that target, and therefore further imbalance, multiple DNA repair pathways. A key protein in the Base Excision Repair (BER) pathway, Apurinic/apyrimidinic endonuclease/ redox factor (APE1/Ref-1 or APE1) plays a major role in the repair of damage caused by chemotherapeutic agents including M and Temozolomide (TMZ), interacts with a number of transcription factors (HIF1-a, p53, AP1, NFkB, etc) to regulate their function through oxidation/reduction (redox) signaling, and is overexpressed in refractory/relapsed MM cells. Furthermore, a reduction in APE1 protein sensitizes MM cells to melphalan indicating that inhibition of this protein may have therapeutic potential in MM. In order to decipher the importance of APE1’s redox and repair functions in MM cells’ response to DNA damage via melphalan and TMZ, we have available to us small molecule APE1 inhibitors that affect only the repair activity or only the redox activity of APE1. The mechanism of action of MLP is primarily via monoadduct leading to DNA interstrand cross-link (ICL) formation which is processed by the Nucleotide Excision Repair (NER) pathway. MLP also causes N7methyl-G and N3methyl-A adduct formation which are repaired by the BER pathway. For these studies, we treated RPMI 8226 cells with several chemotherapeutic agents: M; TMZ, which creates primarily N7methyl-G and N3methyl-A adducts; Methoxyamine (MX), which has been shown to inhibit further processing by the BER pathway; and a small molecule which blocks the redox function of APE1. Our purpose was to overwhelm the DNA repair pathways by causing the accumulation of DNA repair intermediates and inducing apoptosis. M-induced cytotoxicity is enhanced by TMZ (CI=0.08), MX (CI=0.89), and E3330 (CI=0.06), and this effect was synergistic as determined by CalcuSyn software which generates median effect and combinational index (CI) values, with CI<1 indicative of synergy. Using MX to inhibit APE1 in combination with TMZ results in an increase in DNA damage and an increase in apoptosis in 8226 cells. Furthermore, the combination of the redox inhibitor + MX which blocks both functions of APE1 also results in an increase in apoptosis in the MM cells. Further studies include the addition of M to these combinations that are demonstrating an increase in efficacy in MM cells. These results indicate that using these DNA repair-targeted agents in addition to MLP may be a feasible way to increase the effect of the M on MM cells. The potential advantages to patients would be that they would be able to tolerate more treatments and that the combination treatments would be more effective than treatment with M alone. We anticipate that effective modulation of M and/or TMZ will overcome resistance without compromising efficacy and help to alleviate some of the side effects patients have to endure with melphalan treatment. This may be particularly advantageous to the more elderly patients.

Base excision repair pathways of bacteria: new promise for an old problem

2020 ◽  
Vol 12 (4) ◽  
pp. 339-355 ◽  
Author(s):  
Krishna Kurthkoti ◽  
Pradeep Kumar ◽  
Pau Biak Sang ◽  
Umesh Varshney
Keyword(s):  
Immune Response ◽  
Drug Resistance ◽  
Small Molecules ◽  
Base Excision Repair ◽  
Drug Target ◽  
Excision Repair ◽  
Genomic Integrity ◽  
Repair Pathways ◽  
Cellular Pathways ◽  
Base Excision

Infectious diseases continue to be a major cause of human mortality. With the emergence of drug resistance, diseases that were long thought to have been curable by antibiotics are resurging. There is an urgent clinical need for newer antibiotics that target novel cellular pathways to overcome resistance to currently used therapeutics. The base excision repair (BER) pathways of the pathogen restore altered bases and safeguard the genomic integrity of the pathogen from the host's immune response. Although the BER machinery is of paramount importance to the survival of the pathogens, its potential as a drug target is largely unexplored. In this review, we discuss the importance of BER in different pathogenic organisms and the potential of its inhibition with small molecules.

scholarly journals How are base excision DNA repair pathways deployed in vivo?

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 279 ◽  
Author(s):  
Upasna Thapar ◽  
Bruce Demple
Keyword(s):  
Dna Repair ◽  
Base Excision Repair ◽  
Mammalian Cells ◽  
Excision Repair ◽  
Biochemical Level ◽  
Repair Pathways ◽  
Base Excision ◽  
Base Excision Dna Repair

Since the discovery of the base excision repair (BER) system for DNA more than 40 years ago, new branches of the pathway have been revealed at the biochemical level by in vitro studies. Largely for technical reasons, however, the confirmation of these subpathways in vivo has been elusive. We review methods that have been used to explore BER in mammalian cells, indicate where there are important knowledge gaps to fill, and suggest a way to address them.

scholarly journals Inhibitors of DNA Glycosylases as Prospective Drugs

2020 ◽  
Vol 21 (9) ◽  
pp. 3118 ◽  
Author(s):  
Grigory V. Mechetin ◽  
Anton V. Endutkin ◽  
Evgeniia A. Diatlova ◽  
Dmitry O. Zharkov
Keyword(s):  
Clinical Trials ◽  
Base Excision Repair ◽  
Viral Infections ◽  
Excision Repair ◽  
Biochemical Process ◽  
Dna Glycosylases ◽  
Repair Pathway ◽  
Repair Pathways ◽  
Base Excision ◽  
Living Organisms

DNA glycosylases are enzymes that initiate the base excision repair pathway, a major biochemical process that protects the genomes of all living organisms from intrinsically and environmentally inflicted damage. Recently, base excision repair inhibition proved to be a viable strategy for the therapy of tumors that have lost alternative repair pathways, such as BRCA-deficient cancers sensitive to poly(ADP-ribose)polymerase inhibition. However, drugs targeting DNA glycosylases are still in development and so far have not advanced to clinical trials. In this review, we cover the attempts to validate DNA glycosylases as suitable targets for inhibition in the pharmacological treatment of cancer, neurodegenerative diseases, chronic inflammation, bacterial and viral infections. We discuss the glycosylase inhibitors described so far and survey the advances in the assays for DNA glycosylase reactions that may be used to screen pharmacological libraries for new active compounds.

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