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

2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
Guido Frosina

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.

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 862 ◽  
Author(s):  
Alexander Schulz ◽  
Felix Meyer ◽  
Anna Dubrovska ◽  
Kerstin Borgmann

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.


2017 ◽  
Vol 71 (0) ◽  
pp. 0-0
Author(s):  
Ewelina Stelcer ◽  
Magdalena Łukjanow ◽  
Wiktoria Maria Suchorska

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.


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