Departments of Radiation Oncology and Environmental Health Sciences, Rogel Cancer Center and Center for RNA Biomedicine, University of Michigan, Ann Arbor, MI, USA.
DNA Repair (Amst). 2022 Oct;118:103373. doi: 10.1016/j.dnarep.2022.103373. Epub 2022 Jul 19.
Transcription can cause genome instability by promoting R-loop formation but also act as a mutation-suppressing machinery by sensing of DNA lesions leading to the activation of DNA damage signaling and transcription-coupled repair. Recovery of RNA synthesis following the resolution of repair of transcription-blocking lesions is critical to avoid apoptosis and several new factors involved in this process have recently been identified. Some DNA repair proteins are recruited to initiating RNA polymerases and this may expediate the recruitment of other factors that participate in the repair of transcription-blocking DNA lesions. Recent studies have shown that transcription of protein-coding genes does not always give rise to spliced transcripts, opening the possibility that cells may use the transcription machinery in a splicing-uncoupled manner for other purposes including surveillance of the transcribed genome.
转录可以通过促进 R 环形成导致基因组不稳定,但也可以作为一种突变抑制机制,通过感知 DNA 损伤导致 DNA 损伤信号转导和转录偶联修复的激活。转录受阻损伤修复后 RNA 合成的恢复对于避免细胞凋亡至关重要,最近已经确定了几个参与该过程的新因子。一些 DNA 修复蛋白被招募到起始 RNA 聚合酶上,这可能会加速其他参与转录受阻 DNA 损伤修复的因子的招募。最近的研究表明,蛋白质编码基因的转录并不总是产生剪接转录本,这为细胞可能以剪接不偶联的方式利用转录机制用于其他目的(包括对转录基因组的监测)提供了可能性。