RBM15B: A new player in DNA damage response

R-loops, a nucleic acid structure consisting of a DNA:RNA hybrid and a displaced DNA strand, accumulate in proximity to transcriptionally active genomic regions, and their improper removal has deleterious effect on DSB repair. Concordantly, an increasing number of RNA-binding proteins are implicated in DNA double-strand breaks (DSBs) repair. My project focuses on an understudied nuclear RNA-binding protein RBM15B. It has various cellular roles, as it regulates RNA m6A methylation, participates in the XIST-mediated silencing of X chromosome and is involved in RNA splicing. Moreover, RBM15B promotes cancer cell proliferation and is misregulated in various types of cancer. Herein, we provide several lines of evidence implicating RBM15B in DNA damage response. We showed that RBM15B is recruited to laser-microirradiated sites in a PARP1-dependent manner. Moreover, RBM15B is enriched at DSBs as evident by ChIP and biochemical fractionation. Consequently, our preliminary results show that RBM15B regulates DSB repair and affects R-loop levels during DNA damage. Currently, we wish to determine whether the defective DSB repair in RBM15B-deficient cells is functionally related to R-loop misregulation.