Knockdown of alphaII spectrin in normal human cells by siRNA leads to chromosomal instability and decreased DNA interstrand cross-link repair.

Autor: McMahon LW; 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, USA., Zhang P, Sridharan DM, Lefferts JA, Lambert MW
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2009 Apr 03; Vol. 381 (2), pp. 288-93. Date of Electronic Publication: 2009 Feb 13.
DOI: 10.1016/j.bbrc.2009.02.038
Abstrakt: 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.
Databáze: MEDLINE