scholarly journals DNA repair in cancer development and aging

Aging ◽  
2021 ◽  
Author(s):  
Hua Zhao ◽  
Bernard F. Fuemmeler ◽  
Jie Shen
Keyword(s):  
Dna Repair ◽  
Cancer Development ◽  
Development And Aging

scholarly journals Endogenous formaldehyde scavenges cellular glutathione resulting in cytotoxic redox disruption

2020 ◽  
Author(s):  
Carla Umansky ◽  
Agustín Morellato ◽  
Marco Scheidegger ◽  
Matthias Rieckher ◽  
Manuela R. Martinefski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Fanconi Anemia ◽  
Redox Homeostasis ◽  
Thiol Group ◽  
Cellular Damage ◽  
Repair Pathway ◽  
Cellular Redox ◽  
Redox Active ◽  
Development And Aging

AbstractFormaldehyde (FA) is a ubiquitous endogenous and environmental metabolite that is thought to exert cytotoxicity through DNA and DNA-protein crosslinking. We show here that FA can cause cellular damage beyond genotoxicity by triggering oxidative stress, which is prevented by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR). Mechanistically, we determine that endogenous FA reacts with the redox-active thiol group of glutathione (GSH) forming S-hydroxymethyl-GSH, which is metabolized by ADH5 yielding reduced GSH thus preventing redox disruption. We identify the ADH5-ortholog gene in Caenorhabditis elegans and show that oxidative stress also underlies FA toxicity in nematodes. Moreover, we show that endogenous GSH can protect cells lacking the Fanconi Anemia DNA repair pathway from FA, which might have broad implications for Fanconi Anemia patients and for healthy BRCA2-mutation carriers. We thus establish a highly conserved mechanism through which endogenous FA disrupts the GSH-regulated cellular redox homeostasis that is critical during development and aging.

scholarly journals Cyclin A2 promotes DNA repair in the brain during both development and aging

Aging ◽  
2016 ◽  
Vol 8 (7) ◽  
pp. 1540-1570 ◽  
Author(s):  
Patrick E. Gygli ◽  
Joshua C. Chang ◽  
Hamza N. Gokozan ◽  
Fay P. Catacutan ◽  
Theresa A. Schmidt ◽  
...  
Keyword(s):  
Dna Repair ◽  
Cyclin A2 ◽  
Development And Aging ◽  
The Brain

scholarly journals Alteration to the SWI/SNF complex in human cancers

2011 ◽  
Vol 4 (2) ◽  
pp. 89
Author(s):  
Vanessa S. Gordon ◽  
Colin Rogers ◽  
David Reisman
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Cell Adhesion ◽  
Growth Control ◽  
Cellular Growth ◽  
Cancer Development ◽  
Catalytic Subunits ◽  
Cancer Types ◽  
Potential Impact ◽  
The Impact

The SWI/SNF complex is a key catalyst for gene expression and regulates a variety of pathways, many of which have anticancer roles. Its central roles in cellular growth control, DNA repair, differentiation, cell adhesion and development are often targeted, and inactivated, during cancer development and progression. In this review, we will discuss what is known about how SWI/SNF is inactivated, and describe the potential impact of abrogating this complex. BRG1 and BRM are the catalytic subunits which are essential for SWI/SNF function, and thus, it is not surprising that they are lost in a variety of cancer types. As neither gene is mutated when lost, the mechanism of suppression, as well as the impact of potential gene activity restoration, are reviewed.

scholarly journals DNA Damage/Repair Management in Cancers

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1050 ◽  
Author(s):  
Jehad F. Alhmoud ◽  
John F. Woolley ◽  
Ala-Eddin Al Moustafa ◽  
Mohammed Imad Malki
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Dna Damage Repair ◽  
Critical Factor ◽  
Dna Lesions ◽  
Cancer Development ◽  
Dna Damaging Agents ◽  
Damage Repair ◽  
Repair Mechanisms ◽  
Dna Strand

DNA damage is well recognized as a critical factor in cancer development and progression. DNA lesions create an abnormal nucleotide or nucleotide fragment, causing a break in one or both chains of the DNA strand. When DNA damage occurs, the possibility of generated mutations increases. Genomic instability is one of the most important factors that lead to cancer development. DNA repair pathways perform the essential role of correcting the DNA lesions that occur from DNA damaging agents or carcinogens, thus maintaining genomic stability. Inefficient DNA repair is a critical driving force behind cancer establishment, progression and evolution. A thorough understanding of DNA repair mechanisms in cancer will allow for better therapeutic intervention. In this review we will discuss the relationship between DNA damage/repair mechanisms and cancer, and how we can target these pathways.

scholarly journals New perspectives in cancer biology from a study of canonical and non-canonical functions of base excision repair proteins with a focus on early steps

Mutagenesis ◽  
2019 ◽  
Vol 35 (1) ◽  
pp. 129-149 ◽  
Author(s):  
Matilde Clarissa Malfatti ◽  
Giulia Antoniali ◽  
Marta Codrich ◽  
Silvia Burra ◽  
Giovanna Mangiapane ◽  
...  
Keyword(s):  
Dna Repair ◽  
Base Excision Repair ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Excision Repair ◽  
Dna Lesions ◽  
Cancer Development ◽  
Dna Repair Enzymes ◽  
Repair Enzymes ◽  
Base Excision

Abstract Alterations of DNA repair enzymes and consequential triggering of aberrant DNA damage response (DDR) pathways are thought to play a pivotal role in genomic instabilities associated with cancer development, and are further thought to be important predictive biomarkers for therapy using the synthetic lethality paradigm. However, novel unpredicted perspectives are emerging from the identification of several non-canonical roles of DNA repair enzymes, particularly in gene expression regulation, by different molecular mechanisms, such as (i) non-coding RNA regulation of tumour suppressors, (ii) epigenetic and transcriptional regulation of genes involved in genotoxic responses and (iii) paracrine effects of secreted DNA repair enzymes triggering the cell senescence phenotype. The base excision repair (BER) pathway, canonically involved in the repair of non-distorting DNA lesions generated by oxidative stress, ionising radiation, alkylation damage and spontaneous or enzymatic deamination of nucleotide bases, represents a paradigm for the multifaceted roles of complex DDR in human cells. This review will focus on what is known about the canonical and non-canonical functions of BER enzymes related to cancer development, highlighting novel opportunities to understand the biology of cancer and representing future perspectives for designing new anticancer strategies. We will specifically focus on APE1 as an example of a pleiotropic and multifunctional BER protein.

scholarly journals Functional Interaction Between BRCA1 and DNA Repair in Yeast May Uncover a Role of RAD50, RAD51, MRE11A, and MSH6 Somatic Variants in Cancer Development

2018 ◽  
Vol 9 ◽  
Author(s):  
Luisa Maresca ◽  
Samuele Lodovichi ◽  
Alessandra Lorenzoni ◽  
Tiziana Cervelli ◽  
Rossella Monaco ◽  
...  
Keyword(s):  
Dna Repair ◽  
Cancer Development ◽  
Functional Interaction

scholarly journals Assessment on the influence of TLR4 and DNA repair genes in laryngeal cancer susceptibility: a selective examination in a Romanian case control study

2021 ◽  
Vol 29 (1) ◽  
pp. 19-31
Author(s):  
Corina Iulia Cornean ◽  
Violeta Necula ◽  
Marcel Cosgarea ◽  
Alma Aurelia Maniu ◽  
Andreea Catana
Keyword(s):  
Dna Repair ◽  
Laryngeal Cancer ◽  
Case Control Study ◽  
Cancer Susceptibility ◽  
Fold Increase ◽  
Case Control ◽  
Cancer Development ◽  
Individual Risk ◽  
Cancer Evolution ◽  
Control Study

Abstract Background: Tumor characterization through the study of molecular biology has become an invaluable tool in understanding cancer development and evolution due to its relationship with chromosomal mutations, alterations or aberrations. The purpose of this study was to investigate the involvement of genes such as TLR-4 and DNA repair pathways (XRCC1 and XPD) in laryngeal cancer susceptibility in a Romanian population. Method: We performed a case-control study on 157 laryngeal cancer patients and 101 healthy controls. Genetic testing was carried out using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. Results: We identified the Gln allele of the XPDLys751Gln polymorphism as an individual risk factor in laryngeal cancer development (Gln vs Lys, adjusted OR=1.65, 95%CI=1.13–2.40, P=0.008). Subjects with the mutant homozygote variant (Gln/Gln) had a two fold increase in cancer risk (adjusted OR=2.18, 95%CI=1.06–4.47, p=0.028) when compared to the reference wild type genotype (Lys/Lys). Stratification by sex and age, identified males under 62 years as the most susceptible group with an almost three fold risk (adjusted OR=2.94, 95%CI=1.31–6.59, p=0.007) for the dominant model (Lys/Gln+Gln/Gln). No associations were found for TLR-4Thr399Ile, XRCC1Arg194Trp and XRCC1Arg399Gln. Conclusion: The results of the study show that the XPDLys751Gln polymorphism may be among other independent risk factors for developing laryngeal cancer where as TLR-4Thr399Ile, XRCC1Arg194Trp and XRCC1 Arg399Gln show no such association. However, we consider the relative small number of the subjects selected for this analyses a possible limitation towards the real influence the obtain results may pertain in laryngeal cancer evolution.

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