真核生物已经进化出了复杂的机制,通过蛋白感受器、传感器及作用因子的协同作用来进行DNA双链断裂修复(DSBs)。
北京生命科学研究所的戚益军等人研究发现,在拟南芥及人类细胞中,DSB位点附近产生了大小约21个核苷酸的小RNAs。研究人员把这些小RNAs称作对DSB诱导的小RNAs有关的diRNAs。相关论文发表在3月30日的Cell。
在拟南芥中,diRNAs的产生需要PI3激酶ATR,RNA合成酶IV(Pol IV),以及Dicer样蛋白。这些蛋白及Pol V的突变会引起DSB修复效率显著的降低。
而且,在拟南芥中,diRNAs是由Argonaute蛋白2(AGO2)招募来介导DSB的修复。在人类细胞中,敲除Dicer或Ago2同样会降低DSB的修复效率。
研究结果表明,diRNAs介导的DSB修复在人类及植物中是保守的。
因此,diRNAs很能是作为一个引导分子来指向染色体修饰,或者是招募蛋白复合体到DSB位点来帮助修复。(生物谷Deepblue编译)
doi: 10.1016/j.cell.2012.03.002
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A Role for Small RNAs in DNA Double-Strand Break Repair
Wei Wei, Zhaoqing Ba, Min Gao, Yang Wu, Yanting Ma, Simon Amiard, Charles I. White, Jannie Michaela Rendtlew Danielsen, Yun-Gui Yang, Yijun Qi .
Eukaryotes have evolved complex mechanisms to repair DNA double-strand breaks (DSBs) through coordinated actions of protein sensors, transducers, and effectors.Here we show that ~21-nucleotide small RNAs are produced from the sequences in the vicinity of DSB sites in Arabidopsis and in human cells. We refer to these as diRNAs for DSB-induced small RNAs.In Arabidopsis, the biogenesis of diRNAs requires the PI3 kinase ATR, RNA polymerase IV (Pol IV), and Dicer-like proteins. Mutations in these proteins as well as in Pol V cause significant reduction in DSB repair efficiency.In Arabidopsis, diRNAs are recruited by Argonaute 2 (AGO2) to mediate DSB repair. Knock down of Dicer or Ago2 in human cells reduces DSB repair.Our findings reveal a conserved function for small RNAs in the DSB repair pathway.We propose that diRNAs may function as guide molecules directing chro.