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.