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Critical Reviews™ in Eukaryotic Gene Expression

Published 6 issues per year

ISSN Print: 1045-4403

ISSN Online: 2162-6502

The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two preceding years. 2017 Journal Citation Reports (Clarivate Analytics, 2018) IF: 1.6 To calculate the five year Impact Factor, citations are counted in 2017 to the previous five years and divided by the source items published in the previous five years. 2017 Journal Citation Reports (Clarivate Analytics, 2018) 5-Year IF: 2.2 The Immediacy Index is the average number of times an article is cited in the year it is published. The journal Immediacy Index indicates how quickly articles in a journal are cited. Immediacy Index: 0.3 The Eigenfactor score, developed by Jevin West and Carl Bergstrom at the University of Washington, is a rating of the total importance of a scientific journal. Journals are rated according to the number of incoming citations, with citations from highly ranked journals weighted to make a larger contribution to the eigenfactor than those from poorly ranked journals. Eigenfactor: 0.00058 The Journal Citation Indicator (JCI) is a single measurement of the field-normalized citation impact of journals in the Web of Science Core Collection across disciplines. The key words here are that the metric is normalized and cross-disciplinary. JCI: 0.33 SJR: 0.345 SNIP: 0.46 CiteScore™:: 2.5 H-Index: 67

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Localization of the Werner Protein Together with H2AX in γ-Irradiation-Induced Neoplastic Transformed Human Mesenchymal Stem Cells

Volume 27, Issue 1, 2017, pp. 91-97
DOI: 10.1615/CritRevEukaryotGeneExpr.2017019192
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ABSTRACT

The H2A histone family, member X (H2AX), and Werner (WRN) are important proteins for genome and telomere maintenance. WRN has a major role in genome stability, particularly during DNA replication, transcription, recombination, and repair of DNA double-stranded breaks (DSBs) via base excision repair, homologous recombination, or nonhomologous end joining. H2AX plays a part in the rapid, sensitive, cellular response to the ionizing radiation or DNA-damaging chemotherapeutic agents that cause DSBs. This occurs when radiation-induced DSBs trigger the activation of H2AX and begin the damage-repair process. In this study, we investigate the role and localization of WRN together with DNA damage marker H2AX at the radiation-induced damaged sides of both the telomere-immortalized human mesenchymal stem cells (hMSCs) and hMSC-telomere 1 (hMSC-telo1) and in control primary hMSCs. Phosphorylated H2AX and WRN immune staining enabled evaluation of overall genomic integrity and damage/repair. We used peptide nucleic acid−fluorescent in situ hybridization to visualize telomeric damage as a short-term effect. A high-level WRN signal was observed in both primary hMSCs and telomerase-immortalized hMSCs after the cells had been subjected to infrared radiation. Afterward, the irradiation level of the WRN signals decreased considerably, especially in later passages, and WRN was nondetectable in the latest passages of the hMSC Telo1 cells. Contrary to this finding, we found that levels of H2AX phosphorylation in hMSC-telo1 cells increased with time, especially at telomere sides, suggesting that cells with long telomeres and high telomerase activity have the advantage of maintaining genomic integrity. Evaluation of localization of WRN signals demonstrated that WRN does not leave the nucleolus after irradiation. We did not detect the WRN signal at the telomere sides, but we could detect H2AX at the telomeric sides. Thus, our overall data suggest that the WRN protein is not involved in irradiationinduced DNA damage/repair, even at telomeric sides in hMSC and hMSC-telo1.

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