A new mechanism for diRNA mediated DSB repair
A research article entitled “IDN2 interacts with RPA and facilitates DNA double-strand break repair by homologous recombination in Arabidopsis” was published online in The Plant Cell on Feb. 21st, 2017. This work is from Prof. Yijun Qi’s group in the Center for Life Science. In this work, Prof. Qi and colleagues reported that IDN2, a dsRNA-binding protein, interacts with RPA and facilitates the release of RPA from ssDNA tails and subsequent recruitment of RAD51 at DSB sites to promote double-strand break (DSB) repair.
DSB, as the most detrimental form of DNA damage, would lead to gene mutation, genome instability and even cell death, if unrepaired or repaired incorrectly. Cells have evolved sophisticated mechanisms to ensure precise and efficient repair of DSB through the coordinated actions of sensors, transducers, and effectors. Prof. Qi’s group has previously reported a novel class of small RNAs, termed DSB- induced small RNAs or diRNAs, is produced from the sequences around the DSB sites and plays an important role in DSB repair via homologous recombination (HR) (Cell 149: 101-112, 2012). However, how diRNAs mediate DSB repair remains largely unknown.
In this work, Prof. Qi and his colleagues discovered that INVOLVED IN DE NOVO 2 (IDN2), a double-stranded RNA (dsRNA) binding protein, and its two paralogs, IDP (IDN2 Paralog) 1 and IDP2, which are known to be involved in small RNA-directed DNA methylation, are required for DSB repair in Arabidopsis. They found that IDN2 interacted with the heterotrimeric replication protein A (RPA) complex. More importantly, depletion of IDN2 or the diRNA-binding ARGONAUTE 2 (AGO2) led to increased accumulation of RPA at DSB sites and mislocalization of the recombination factor RAD51. These findings support a model in which IDN2 interacts with RPA and facilitates the release of RPA from ssDNA tails and subsequent recruitment of RAD51 at DSB sites to promote DSB repair.
Ph.D student Mingming Liu from the PTN Joint Graduate Program is the first author of this article. Dr. Zhaoqing Ba made a great contribution at the early stage of this work. This work was supported by grants from National Key Research and Development Program of China, National Science Foundation of China and Tsinghua-Peking Joint Center of Life Sciences.
