Shkreta Lulzim, Chabot Benoit
Microbiologie et d'Infectiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada.
Biomolecules. 2015 Oct 29;5(4):2935-77. doi: 10.3390/biom5042935.
The number of factors known to participate in the DNA damage response (DDR) has expanded considerably in recent years to include splicing and alternative splicing factors. While the binding of splicing proteins and ribonucleoprotein complexes to nascent transcripts prevents genomic instability by deterring the formation of RNA/DNA duplexes, splicing factors are also recruited to, or removed from, sites of DNA damage. The first steps of the DDR promote the post-translational modification of splicing factors to affect their localization and activity, while more downstream DDR events alter their expression. Although descriptions of molecular mechanisms remain limited, an emerging trend is that DNA damage disrupts the coupling of constitutive and alternative splicing with the transcription of genes involved in DNA repair, cell-cycle control and apoptosis. A better understanding of how changes in splice site selection are integrated into the DDR may provide new avenues to combat cancer and delay aging.
近年来，已知参与DNA损伤反应（DDR）的因子数量大幅增加，其中包括剪接和可变剪接因子。虽然剪接蛋白和核糖核蛋白复合物与新生转录本的结合通过阻止RNA/DNA双链体的形成来防止基因组不稳定，但剪接因子也会被招募到DNA损伤位点或从这些位点移除。DDR的第一步促进剪接因子的翻译后修饰，以影响其定位和活性，而更多下游的DDR事件则改变它们的表达。尽管对分子机制的描述仍然有限，但一个新出现的趋势是，DNA损伤会破坏组成型和可变剪接与参与DNA修复、细胞周期控制和细胞凋亡的基因转录之间的偶联。更好地理解剪接位点选择的变化是如何整合到DDR中的，可能会为对抗癌症和延缓衰老提供新途径。
