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Tudor-interacting repair regulator (TIRR) is an RNA-binding protein and a negative regulator of the DNA-repair factor p53-binding protein 1 (53BP1). In non-damage conditions, TIRR is bound to 53BP1. After DNA damage, TIRR and 53BP1 dissociate, and 53BP1 binds the chromatin at the double-strand break (DSB) to promote non-homologous end joining (NHEJ)-mediated repair. However, the exact mechanistic details of this dissociation after damage are unknown. Increasing evidence has implicated RNA as a crucial factor in the DNA damage response (DDR). Here, we show that RNA can separate TIRR/53BP1. Specifically, RNA with a hairpin secondary structure, transcribed at the DSB by RNA polymerase II (RNAPII), promotes TIRR/53BP1 complex separation. This hairpin RNA binds to the same residues on TIRR as 53BP1. Our results uncover a role of DNA-damage-derived RNA in modulating a protein-protein interaction and contribute to our understanding of DSB repair.

Original publication

DOI

10.1016/j.celrep.2022.111526

Type

Journal article

Journal

Cell Rep

Publication Date

25/10/2022

Volume

41

Keywords

53BP1, CP: Molecular biology, DARTs, DNA damage, FISH-PLA, NHEJ, RNA, TIRR, dilncRNA, double-strand breaks, hairpin, DNA Breaks, Double-Stranded, RNA, RNA Polymerase II, Tumor Suppressor Protein p53, Protein Binding, Tumor Suppressor p53-Binding Protein 1, DNA Repair, DNA End-Joining Repair, Chromatin, RNA-Binding Proteins, DNA