Why are RNA processing factors recruited to DNA double-strand breaks?

Abstract

DNA double-strand break (DSB) induction leads to local transcriptional silencing at damage sites, raising the question: Why are RNA processing factors (RPFs), including splicing factors, rapidly recruited to these sites? Recent findings show that DSBs cluster in a chromatin compartment termed the 'D compartment', where DNA damage response (DDR) genes relocate and undergo transcriptional activation. Here, we propose two non-mutually exclusive models to elucidate the rationale behind the recruitment of RPFs to DSB sites. First, RPFs circulate through the D compartment to process transcripts of the relocated DDR genes. Second, the D compartment serves as a 'post-translational modifications (PTMs) hub', altering RPF activity and leading to the production of unique DNA damage-induced transcripts, which are essential for orchestrating the DDR.