Knockdown of alphaII spectrin in normal human cells by siRNA leads to chromosomal instability and decreased DNA interstrand cross-link repair
Nonerythroid alpha-spectrin (alphaIISp) is a structural protein involved in repair of DNA interstrand cross-links and is deficient in cells from patients with Fanconi anemia (FA), which are defective in ability to repair cross-links. In order to further demonstrate the importance of the role that al...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2009-04, Vol.381 (2), p.288-293 |
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| container_title | Biochemical and biophysical research communications |
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| creator | McMahon, Laura W Zhang, Pan Sridharan, Deepa M Lefferts, Joel A Lambert, Muriel W |
| description | Nonerythroid alpha-spectrin (alphaIISp) is a structural protein involved in repair of DNA interstrand cross-links and is deficient in cells from patients with Fanconi anemia (FA), which are defective in ability to repair cross-links. In order to further demonstrate the importance of the role that alphaIISp plays in normal human cells and in the repair defect in FA, alphaIISp was knocked down in normal cells using siRNA. Depletion of alphaIISp in normal cells by siRNA resulted in chromosomal instability and cellular hypersensitivity to DNA interstrand cross-linking agents. An increased number of chromosomal aberrations were observed and, following treatment with a DNA interstrand cross-linking agent, mitomycin C, cells showed decreased cell growth and survival and decreased formation of damage-induced alphaIISp and XPF nuclear foci. Thus depletion of alphaIISp in normal cells leads to a number of defects observed in FA cells, such as chromosome instability and a deficiency in cross-link repair. |
| doi_str_mv | 10.1016/j.bbrc.2009.02.038 |
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In order to further demonstrate the importance of the role that alphaIISp plays in normal human cells and in the repair defect in FA, alphaIISp was knocked down in normal cells using siRNA. Depletion of alphaIISp in normal cells by siRNA resulted in chromosomal instability and cellular hypersensitivity to DNA interstrand cross-linking agents. An increased number of chromosomal aberrations were observed and, following treatment with a DNA interstrand cross-linking agent, mitomycin C, cells showed decreased cell growth and survival and decreased formation of damage-induced alphaIISp and XPF nuclear foci. 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| ispartof | Biochemical and biophysical research communications, 2009-04, Vol.381 (2), p.288-293 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Carrier Proteins - genetics Carrier Proteins - physiology Cell Line, Tumor Chromosomal Instability - genetics Cross-Linking Reagents - pharmacology DNA - drug effects DNA - genetics DNA Repair - genetics Fanconi Anemia - genetics Gene Knockdown Techniques Humans Microfilament Proteins - genetics Microfilament Proteins - physiology RNA, Small Interfering - genetics Transfection |
| title | Knockdown of alphaII spectrin in normal human cells by siRNA leads to chromosomal instability and decreased DNA interstrand cross-link repair |
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