Differential cellular responses to exogenous DNA in mammalian cells and its effect on oligonucleotide-directed gene modification
| Autor: | V Alexeev, Kyonggeun Yoon, O Igoucheva |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
DNA Replication
DNA Repair Swine DNA damage DNA repair Oligonucleotides Cell Cycle Proteins Ataxia Telangiectasia Mutated Proteins Protein Serine-Threonine Kinases Biology Kidney Transfection Cell Line chemistry.chemical_compound Genetics Animals Protein–DNA interaction Molecular Biology Regulation of gene expression Oligonucleotide Gene Expression Profiling Tumor Suppressor Proteins DNA Molecular biology Proliferating cell nuclear antigen DNA-Binding Proteins DNA Repair Enzymes Gene Expression Regulation chemistry biology.protein LLC-PK1 Cells Molecular Medicine Exogenous DNA DNA Damage Signal Transduction |
| Zdroj: | Gene Therapy. 13:266-275 |
| ISSN: | 1476-5462 0969-7128 |
| DOI: | 10.1038/sj.gt.3302643 |
| Popis: | Transient transfection has been widely used in many biological applications including gene regulation and DNA repair, but, so far, little attention has been paid to cellular responses induced by the transfected DNA. Here, we report that double-stranded (ds) DNA introduced into mammalian cells induced expression of a variety of genes involved in DNA damage signaling and DNA repair. The expression profile of the induced genes was highly dependent on the cell type, suggesting interactions between exogenous dsDNA and cellular proteins. Moreover, each cell line elicited a markedly different level of intrinsic cellular responses to the introduced dsDNA. Furthermore, the presence of single-stranded oligonucleotides or short duplexes consisting of two complementary oligonucleotides did not affect cellular response, indicating that the induction was highly dependent on the structure and length of exogenous DNA. The extent of induction of DNA damage, signaling and DNA repair activities correlated to episomal and chromosomal gene correction frequencies. In addition, the presented data indicate that the presence of exogenous dsDNA triggered a DNA damage response by activation of ATR (ataxia telangiectasia-Rad3-related) but not ATM (ataxia telangiectasia mutated) pathway. |
| Databáze: | OpenAIRE |
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