Dickey Jennifer S, Zemp Franz J, Altamirano Alvin, Sedelnikova Olga A, Bonner William M, Kovalchuk Olga
Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Radiat Prot Dosimetry. 2011 Feb;143(2-4):264-9. doi: 10.1093/rpd/ncq470. Epub 2010 Dec 23.
Upon DNA double-strand break (DSB) formation, hundreds of H2AX molecules in the chromatin flanking the break site are phosphorylated on serine residue 139, termed gamma-H2AX, so that virtually every DSB site in a nucleus can be visualised within 10 min of its formation using an antibody to gamma-H2AX. One application of this sensitive assay is to examine the induction of DNA double-strand damage in subtle non-targeted cellular effects such as the bystander effect. Here whether microRNA (miRNA) serve as a primary signalling mechanism for bystander effect propagation by comparing matched human colon carcinoma cell lines with wild-type or depleted levels of mature miRNAs was investigated. No major differences were found in the levels of induced gamma-H2AX foci in the tested cell lines, indicating that though miRNAs play a role in bystander effect manifestation, they appear not to be the primary bystander signalling molecules in the formation of bystander effect-induced DSBs.
在DNA双链断裂（DSB）形成时，断裂位点两侧染色质中的数百个H2AX分子在丝氨酸残基139处被磷酸化，称为γ-H2AX，因此使用抗γ-H2AX抗体可在其形成后10分钟内可视化细胞核内几乎每个DSB位点。这种灵敏检测方法的一个应用是检测微妙的非靶向细胞效应（如旁观者效应）中DNA双链损伤的诱导情况。在此，通过比较具有野生型或成熟miRNA水平降低的匹配人结肠癌细胞系，研究了微小RNA（miRNA）是否作为旁观者效应传播的主要信号传导机制。在测试的细胞系中，诱导的γ-H2AX灶水平未发现重大差异，这表明尽管miRNA在旁观者效应表现中起作用，但它们似乎不是旁观者效应诱导的DSB形成中的主要旁观者信号分子。
