McMahon Laura W, Zhang Pan, Sridharan Deepa M, Lefferts Joel A, Lambert Muriel W
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.
Biochem Biophys Res Commun. 2009 Apr 3;381(2):288-93. doi: 10.1016/j.bbrc.2009.02.038. Epub 2009 Feb 13.
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.
非红细胞α-血影蛋白（αIISp）是一种参与DNA链间交联修复的结构蛋白，在范可尼贫血（FA）患者的细胞中缺乏，这些细胞修复交联的能力存在缺陷。为了进一步证明αIISp在正常人类细胞中的作用以及在FA修复缺陷中的重要性，使用小干扰RNA（siRNA）在正常细胞中敲低αIISp。通过siRNA使正常细胞中的αIISp缺失导致染色体不稳定以及细胞对DNA链间交联剂超敏。观察到染色体畸变数量增加，并且在用DNA链间交联剂丝裂霉素C处理后，细胞显示出细胞生长和存活减少以及损伤诱导的αIISp和XPF核灶形成减少。因此，正常细胞中αIISp的缺失导致在FA细胞中观察到的许多缺陷，如染色体不稳定和交联修复缺陷。
