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

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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DOI:
10.1016/j.bbrc.2009.02.038
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发表时间:
2009-04-03
影响因子:
3.1
通讯作者:
Lambert, Muriel W.
Lambert, Muriel W.
中科院分区:
生物学4区
文献类型:
--
作者:
McMahon, Laura W.;Zhang, Pan;Sridharan, Deepa M.;Lefferts, Joel A.;Lambert, Muriel W.

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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)患者的细胞中存在缺陷,其修复交联的能力有缺陷。为了进一步证明αIISp在正常人细胞中以及在FA的修复缺陷中所起的作用的重要性,使用siRNA在正常细胞中敲低αIISp。通过siRNA消耗正常细胞中的αIISp导致染色体不稳定和细胞对DNA链间交联剂的超敏反应。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,细胞显示细胞生长和存活减少,并且损伤诱导的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,例如染色体不稳定性和交联修复缺陷。
Nonerythroid α-spectrin (αIISp) 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 αIISp plays in normal human cells and in the repair defect in FA, αIISp was knocked down in normal cells using siRNA. Depletion of αIISp 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 αIISp and XPF nuclear foci. Thus depletion of αIISp 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: 10.1006/bbrc.1996.6008
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