scholarly journals The maintenance of genetic stability of embryonic and induced pluripotent stem cells during anticancer therapies

2017 ◽  
Vol 71 (0) ◽  
pp. 0-0
Author(s):  
Ewelina Stelcer ◽  
Magdalena Łukjanow ◽  
Wiktoria Maria Suchorska
Keyword(s):  
Stem Cells ◽  
Dna Repair ◽  
Regenerative Medicine ◽  
Ionizing Radiation ◽  
Genetic Stability ◽  
Excision Repair ◽  
Dna Repair Mechanisms ◽  
Differentiated Cells ◽  
Undifferentiated Cells ◽  
Repair Mechanisms

Regenerative medicine is a very rapidly developing discipline. Its progress contributes to elongated life expectancy and improved quality of life of patients suffering from so far incurable diseases. Stem cells (SCs) are undifferentiated cells that are able to undergo unlimited number of cell divisions and differentiation into specialized cells. Therapies based on SCs constitute a relatively new and promising approach in regenerative medicine. Radiotherapy is the most often used method in the treatment of cancer. In the future, the usage of SCs will be connected with the inevitable exposure of SCs to ionizing radiation during both treatment and diagnosis. The issue of genetic stability of SCs and cells differentiated from them is crucial, particularly regarding the application of these cells in clinical practice. It is important to emphasize that differentiated and undifferentiated cells possess different cell cycle, metabolism, initial level of reactive oxygen species, DNA repair mechanisms, susceptibility to apoptosis and frequency of mutations. All these factors contribute to the distinct radiosensitivity of SCs and differentiated cells. The aim of this study was to present the latest literature data concerning DNA repair mechanisms in pluripotent SCs (Homologous Recombination, Non-homologous End Joining, Mismatch Repair, Base Excision Repair and Nucleotide Excision Repair) in response to the influence of cyto- and genotoxic agents, such as ionizing radiation and chemotherapeutics. Evaluation the efficacy of DNA repair mechanisms is relevant for pluripotent SCs, because ineffective DNA repair mechanisms may result in the accumulation of mutations and, consequently, to cancer.

scholarly journals The Bright and the Dark Sides of DNA Repair in Stem Cells

2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
Guido Frosina
Keyword(s):  
Stem Cells ◽  
Dna Repair ◽  
Somatic Mutations ◽  
High Grade ◽  
Genetic Damage ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms ◽  
Stem And Progenitor Cells ◽  
The Subject ◽  
Intense Research

DNA repair is a double-edged sword in stem cells. It protects normal stem cells in both embryonic and adult tissues from genetic damage, thus allowing perpetuation of intact genomes into new tissues. Fast and efficient DNA repair mechanisms have evolved in normal stem and progenitor cells. Upon differentiation, a certain degree of somatic mutations becomes more acceptable and, consequently, DNA repair dims. DNA repair turns into a problem when stem cells transform and become cancerous. Transformed stem cells drive growth of a number of tumours (e.g., high grade gliomas) and being particularly resistant to chemo- and radiotherapeutic agents often cause relapses. The contribution of DNA repair to resistance of these tumour-driving cells is the subject of intense research, in order to find novel agents that may sensitize them to chemotherapy and radiotherapy.

scholarly journals Cancer Stem Cells and Radioresistance: DNA Repair and Beyond

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 862 ◽  
Author(s):  
Alexander Schulz ◽  
Felix Meyer ◽  
Anna Dubrovska ◽  
Kerstin Borgmann
Keyword(s):  
Stem Cells ◽  
Dna Repair ◽  
Cancer Stem Cells ◽  
Radiation Oncology ◽  
Prognostic Value ◽  
Molecular Mechanisms ◽  
Clinical Findings ◽  
Cell Reprogramming ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms

The current preclinical and clinical findings demonstrate that, in addition to the conventional clinical and pathological indicators that have a prognostic value in radiation oncology, the number of cancer stem cells (CSCs) and their inherent radioresistance are important parameters for local control after radiotherapy. In this review, we discuss the molecular mechanisms of CSC radioresistance attributable to DNA repair mechanisms and the development of CSC-targeted therapies for tumor radiosensitization. We also discuss the current challenges in preclinical and translational CSC research including the high inter- and intratumoral heterogeneity, plasticity of CSCs, and microenvironment-stimulated tumor cell reprogramming.

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 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.

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