The RNA Splicing Response to DNA Damage

Biomolecules

Lulzim Shkreta²  Benoit Chabot¹  Wolf-Dietrich Heyer²  Thomas Helleday² 

[1] Département de Microbiologie et d’Infectiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada; E-Mail

关键词: DNA damage response;    R-loops;    RNA binding proteins;    pre-mRNA;    splicing factors;    alternative splicing;    splice site selection;    chromatin;    transcription;    signal transduction;   

DOI  :  10.3390/biom5042935

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.