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Salzano A Kochiashvili N Nergadze SG Khoriauli L Smirnova A Ruiz-Herrera A Mondello C Giulotto E 《DNA Repair》2009,8(1):19-28
Gene amplification, a key mechanism for oncogene activation and drug resistance in tumour cells, involves the generation and joining of DNA double-strand breaks. Amplified DNA can be carried either on intra-chromosomal arrays or on extra-chromosomal elements (double minutes). We previously showed that, in rodent cells deficient in DNA-PKcs, intra-chromosomal amplification is significantly enhanced. In the present work, we studied gene amplification in human HeLa cell lines in which the expression of the DNA-PKcs gene was constitutively inhibited by shRNAs. These cell lines showed an increased sensitivity to ionizing radiations, an enhanced frequency of chromosomal aberrations and an increased rate of occurrence of methotrexate resistant colonies compared to the control cell lines (6-18 times). The main mechanism of resistance to methotrexate was extra-chromosomal amplification of the dihydrofolate reductase gene. These results indicate that, in human cells, inhibition of DNA-PKcs gene expression favours gene amplification occurring via the production of double minutes. In addition, they show that cell lines constitutively expressing shRNAs are good model systems to study the role of specific functions in gene amplification. 相似文献
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Darul Romane Gavashelishvili Alexander Saveljev Alexander P. Seryodkin Ivan V. Linnell John D. C. Okarma Henryk Bagrade Guna Ornicans Aivars Ozolins Janis Männil Peep Khorozyan Igor Melovski Dime Stojanov Aleksandar Trajçe Aleksandër Hoxha Bledi Dvornikov Mikhail G. Galsandorj Naranbaatar Okhlopkov Innokentiy Mamuchadze Jimsher Yarovenko Yuriy A. Akkiev Muzigit I. Sulamanidze Giorgi Kochiashvili Vazha Şahin Mehmet Kürşat Trepet Sergey A. Pkhitikov Alim B. Farhadinia Mohammad S. Godoy Jose A. Jászay Tomáš Ratkiewicz Mirosław Schmidt Krzysztof 《Journal of Mammalian Evolution》2022,29(1):51-62
Journal of Mammalian Evolution - We studied the relationship between the variability and contemporary distribution of pelage phenotypes in one of most widely distributed felid species and an array... 相似文献
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