Knockdown of {alpha}II spectrin in normal human cells by siRNA leads to chromosomal instability and decreased DNA interstrand cross-link repair
- Department of Pathology and Laboratory Medicine, UMDNJ - New Jersey Medical School and the Graduate School of Biomedical Sciences, 185 South Orange Avenue, Newark, NJ 07103 (United States)
Nonerythroid {alpha}-spectrin ({alpha}IISp) 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 {alpha}IISp plays in normal human cells and in the repair defect in FA, {alpha}IISp was knocked down in normal cells using siRNA. Depletion of {alpha}IISp 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 {alpha}IISp and XPF nuclear foci. Thus depletion of {alpha}IISp in normal cells leads to a number of defects observed in FA cells, such as chromosome instability and a deficiency in cross-link repair.
- OSTI ID:
- 21255962
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 381, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2009.02.038; PII: S0006-291X(09)00295-2; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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