由紫外线辐射引入到DNA内的损伤会阻断转录，这是一个也被用来下调蛋白丰度的机制。这一DNA损伤反应已知也会影响转录体剪接，而这项研究则提出一个可能的机制。Maria Tresini及同事发现，紫外线损伤造成含有U2和U5 snRNP的核心剪接体的染色质置换，因此，会形成含有新转录体的R-环，后者以前馈方式激活DNA损伤反应激酶ATM，来影响剪接体动态和另类剪接。
原文对照：
In response to DNA damage, tissue homoeostasis is ensured by protein networks promoting DNA repair, cell cycle arrest or apoptosis. DNA damage response signalling pathways coordinate these processes, partly by propagating gene-expression-modulating signals. DNA damage influences not only the abundance of messenger RNAs, but also their coding information through alternative splicing. Here we show that transcription-blocking DNA lesions promote chromatin displacement of late-stage spliceosomes and initiate a positive feedback loop centred on the signalling kinase ATM. We propose that initial spliceosome displacement and subsequent R-loop formation is triggered by pausing of RNA polymerase at DNA lesions. In turn, R-loops activate ATM, which signals to impede spliceosome organization further and augment ultraviolet-irradiation-triggered alternative splicing at the genome-wide level. Our findings define R-loop-dependent ATM activation by transcription-blocking lesions as an important event in the DNA damage response of non-replicating cells, and highlight a key role for spliceosome displacement in this process.
原文地址：http://www.nature.com/nature/journal/v523/n7558/full/nature14512.html