title: The RNA Splicing Response to DNA Damage.
abstract: 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.
authors.affiliation: Microbiologie et d'Infectiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada. lulzim.shkreta@usherbrooke.ca.
authors.forename: Lulzim
authors.initials: L
authors.lastname: Shkreta
authors.affiliation: Microbiologie et d'Infectiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada. benoit.chabot@usherbrooke.ca.
authors.forename: Benoit
authors.initials: B
authors.lastname: Chabot
mesh_terms: D000818:Animals; D004249:DNA Damage; D006801:Humans; D011499:Protein Processing, Post-Translational; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016601:RNA-Binding Proteins
keywords: DNA damage response; R-loops; RNA binding proteins; alternative splicing; chromatin; pre-mRNA; signal transduction; splice site selection; splicing factors; transcription