Review of 53bp1 inhibitory mechanism in

This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract DNA is one of the prime molecules, and its stability is of utmost importance for proper functioning and existence of all living systems. Genotoxic chemicals and radiations exert adverse effects on genome stability. To counteract these lesions, organisms have developed a number of highly conserved repair mechanisms such as photoreactivation, base excision repair BERnucleotide excision repair NERand mismatch repair MMR.

Review of 53bp1 inhibitory mechanism in

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This article has been cited by other articles in PMC. Abstract Background It is widely accepted that DNA double-strand breaks DSBs and their misrepair in stem cells are critical events in the multistage origination of various leukemias and tumors, including gliomas.

OMIM Entry - + - CHECKPOINT KINASE 2, S. POMBE, HOMOLOG OF; CHEK2

Results Microwaves from mobile phones inhibited formation of 53BP1 foci in human primary fibroblasts and mesenchymal stem cells. These data parallel our previous findings for human lymphocytes. Exposure at MHz did not inhibit 53BP1 foci in differentiated cells, either fibroblasts or lymphocytes, whereas some effects were seen in stem cells at MHz.

Contrary to fibroblasts, stem cells did not adapt to chronic exposure during 2 weeks. Conclusions The strongest microwave effects were always observed in stem cells. This result may suggest both significant misbalance in DSB repair and severe stress response.

Our findings that stem cells are most sensitive to microwave exposure and react to more frequencies than do differentiated cells may be important for cancer risk assessment and indicate that stem cells are the most relevant cellular model for validating safe mobile communication signals.

However, effects of prolonged exposure to nonthermal NT MWs at intensities comparable with those of mobile phones have also been observed in many studies that indicate a relationship between NT MW exposure and permeability of the brain—blood barrier Nittby et al.

The data obtained by the comet assay Diem et al. Experimental data have indicated that the NT MW effects occur depending on several physical parameters, including carrier frequency, polarization, modulation, and intermittence Belyaev a.

Differences in these physical parameters and biological variables, including genetic background and physiologic state, may explain various outcomes of studies with NT MWs Belyaev b ; Huss et al.

For a long time stem cells have been considered an important cellular target for origination of cancer—both tumors and leukemia Feinberg et al. Gliomas are believed to originate from stem cells in the brain Altaner DNA double-strand breaks DSBs and their misrepair are critical molecular events resulting in chromosomal aberrations, which have often been associated with origination of various leukemias and tumors, including gliomas Fischer and Meese Surprisingly, the data obtained in that study by the neutral comet assay suggested that prolonged exposure time abolished the DSB formation observed at the shorter exposure time.

Furthermore, the neutral comet assay has limited applicability to detect DSBs because similar increases in comet tails may be also caused by nongenotoxic effects that imply changes in chromatin conformation, such as relaxation of DNA loops Belyaev et al.

Analysis of DNA repair foci is currently accepted as the most sensitive and specific technique for measuring DSBs in untreated cells, as well as in cells exposed to cytotoxic agents Bocker and Iliakis ; Bonner et al. By analysis of the DNA repair foci in normal human fibroblasts, we were able to detect DSBs induced by a very low dose of ionizing radiation, 1 cGy, which results in only 0.

Review of 53bp1 inhibitory mechanism in

This inhibition might be caused by a decrease in accessibility of DSBs to proteins because of stress-induced chromatin condensation Belyaev et al. Inability to form DNA repair foci has been correlated to radiosensitivity, genomic instability, and other repair defects Bassing et al.

Inhibition of DSB repair may lead to chromosomal aberrations by either illegitimate recombination events Bassing and Alt or reduced functionality of nonhomologous end-joining Fischer and Meese Therefore, if similar effects on endogenous DNA repair foci are detected in stem cells, this might provide a direct mechanistic link to the epidemiologic data showing association of MW exposure with increased cancer risk.

The differences in the DSB repair pathways between mouse and human stem cells have been described Banuelos et al. In general, the comparisons of stem cells across species suggest that significant differences may be observed, so extrapolation from animal stem cell models to human health risk assessment should be done with care Brons et al.

For the present study, we chose human adipose-tissue derived mesenchymal stem cells MSCs. This cell type displays multipotency with the ability under the correct conditions to differentiate into lineages that cover a wide range of organs and tissues, such as bone, fat, cartilage, muscle, lung, skin, hepatocytes, and neurons Bunnell et al.

Materials and Methods

Of note, MSCs are at higher risk of malignant transformation than are embryonic stem cells Soltysova et al. In previous studies we investigated MW effects on lymphocytes. However, it would be of interest to analyze the response of human stem cells, which are usually exposed to the mobile phone MWs along with differentiated human cells such as lymphocytes and fibroblasts.

Human MSCs separated from adipose tissue of two healthy persons described previously by Kucerova et al. Briefly, exposures were performed using two specially designed installations, each based on a transverse electromagnetic line cell TEM-cell and a test mobile phone.

The output of each phone was connected by the coaxial cable to the corresponding TEM-cell. Taking into account all possible uncertainties, the SAR values at all locations within exposed samples were always well below thermal effects. Temperature was measured in the MW-exposed samples before, during, and after exposure with a precision of 0.

No changes in temperature were induced in the samples during exposures. In addition to MWs, mobile phones emit electromagnetic fields of extremely low frequency ELF that can also contribute to the exposure effects Weisbrot et al.

To avoid eventual effects of ELF exposure, the test mobile phones were situated 1 m from the CO2 incubator containing exposed samples.───── 総 説 ─────.

p53とヒトのがん. 東北大学加齢医学研究所 癌化学療法研究分野 東北大学病院 腫瘍内科. In response to DNA damage and replication blocks, cells prevent cell cycle progression through the control of critical cell cycle regulators. To investigate checkpoint conservation, Matsuoka et al. () used PCR and database analysis to identify CHK2, the mammalian homolog of Saccharomyces.

Research Microwaves from Mobile Phones Inhibit 53BP1 Focus Formation in Human Stem Cells More Strongly Than in Differentiated Cells: Possible Mechanistic. Research Microwaves from Mobile Phones Inhibit 53BP1 Focus Formation in Human Stem Cells More Strongly Than in Differentiated Cells: Possible Mechanistic Link to Cancer Risk Eva Markovà.

助教(特命) 城﨑 幸介 Tamura I, Shirafuta Y, Jozaki K, Kajimura T, Shinagawa M, Maekawa R, Taketani T, Asada H, Sato S, Tamura H, Sugino N. Novel function of a transcription factor WT1 in regulating decidualization in human endometrial stromal cells and its molecular mechanism. The carcinogenesis of non-small cell lung carcinoma has been found to associate with activating and resistant mutations in the tyrosine kinase domain of specific oncogenes.

53BP1 inhibitors, derived from the modification of wild-type ubiquitin, as well as compositions comprising the inhibitors and methods of using same are provided. The inhibitors can be used in combination with gene editing systems.

OMIM Entry - * - TUMOR PROTEIN p53; TP53