Project : Identification of novel DDR genes
In the aim of identifying new DDR-responsive genes, we have developped an in vitro screen using protein extracts derived from Xenopus eggs and identified five genes candidates. One of these is the Ddx19 RNA helicase, previously implicated in the export of the mRNA from the nucleus into the cytoplasm. We have shown that Ddx19 translocates from the nuclear peryphery into the nucleus upon DNA damage (Figure 4). We have also unveiled a novel nuclear function for this enzyme in the resolution of aberrant RNA:DNA hybrid structures formed upon conflicts between replication and transcription, the so called R-loops (Hodroj et al., EMBO J 2017). We are now in the process of understanding the molecular basis of this novel function for the Ddx19 helicase.
Figure 1. Model showing the ATR-dependent Ddx19 function in nuclear R-loop resolution.