3月22日，國際著名雜志Cell在線刊登了北京生命科學研究所戚益軍博士實驗室的最新研究成果“A Role for Small RNAs in DNA Double-Strand Break Repair,，”文章中，研究者報道了一類在DNA雙鏈斷裂（double strand break,， DSB）修復中起到重要作用的小分子RNA。
DNA雙鏈斷裂可以導致突變,、基因組不穩(wěn)定性和細胞死亡,，因此DNA雙鏈斷裂的修復對保持基因組的完整性和細胞的存活至關(guān)重要。真核生物具有復雜的DNA雙鏈斷裂修復通路,，這些通路涉及一系列蛋白質(zhì)的協(xié)調(diào)參與,。戚益軍研究組利用DNA雙鏈斷裂修復報告系統(tǒng)在擬南芥中發(fā)現(xiàn)，小分子RNA可以特異性地從DNA雙鏈斷裂位點的鄰近序列產(chǎn)生,。這些小分子RNA被命名為diRNA （DSB-induced small RNA）,。進一步研究發(fā)現(xiàn)，diRNA的產(chǎn)生依賴于PI3激酶ATR,，RNA聚合酶IV和DCL（Dicer-like）,，其產(chǎn)生后被AGO2蛋白招募而起作用。在擬南芥中,，這些因子的突變可導致DNA雙鏈斷裂修復效率的下降,。戚益軍研究組和中科院北京基因組研究所楊運桂研究組合作研究發(fā)現(xiàn)，diRNA也可在人細胞中產(chǎn)生并且參與DNA雙鏈斷裂的修復,。這些研究結(jié)果表明小分子RNA在真核生物DNA雙鏈斷裂修復過程中具有保守的重要功能,，并為人們對DNA雙鏈斷裂修復機理的認識提供了突破性的新概念。
博士研究生韋薇和巴肇慶為該論文的共同第一作者,。參與該論文研究的還有技術(shù)員吳楊和馬妍亭,，中科院北京基因組研究所的楊運桂研究員，高敏博士和Jannie Danielsen博士,，法國Clermont Université的Charles White教授和Simon Amiard博士,。戚益軍博士為該論文的通訊作者。該項研究由科技部973項目資助,。（生物谷Bioon.com）
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 chromatin modifications or the recruitment of protein complexes to DSB sites to facilitate repair.
