DNA 双链断裂产生的 RNA 导致 TIRR/53BP1 复合物解离。
DNA double-strand break-derived RNA drives TIRR/53BP1 complex dissociation.
机构信息
Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK.
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science, and Technology, Baldiri Reixac 10-12, 08028 Barcelona, Spain; Department of Biochemistry and Molecular Biology. University of Barcelona, 08028 Barcelona, Spain.
出版信息
Cell Rep. 2022 Oct 25;41(4):111526. doi: 10.1016/j.celrep.2022.111526.
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.
Tudor 相互作用修复调节因子（TIRR）是一种 RNA 结合蛋白，也是 DNA 修复因子 p53 结合蛋白 1（53BP1）的负调节剂。在非损伤条件下，TIRR 与 53BP1 结合。在 DNA 损伤后，TIRR 和 53BP1 解离，53BP1 结合双链断裂（DSB）处的染色质，以促进非同源末端连接（NHEJ）介导的修复。然而，损伤后这种解离的确切机制细节尚不清楚。越来越多的证据表明 RNA 是 DNA 损伤反应（DDR）的关键因素。在这里，我们表明 RNA 可以分离 TIRR/53BP1。具体而言，由 RNA 聚合酶 II（RNAPII）在 DSB 处转录的具有发夹二级结构的 RNA 促进 TIRR/53BP1 复合物分离。这种发夹 RNA 与 53BP1 结合在 TIRR 上的相同残基上。我们的结果揭示了 DNA 损伤衍生 RNA 在调节蛋白质-蛋白质相互作用中的作用，并有助于我们理解 DSB 修复。
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