title: Is post-transcriptional stabilization, splicing and translation of selective mRNAs a key to the DNA damage response?
abstract: In response to DNA damage, cells activate a complex, kinase-based signaling network that consist of two components--a rapid phosphorylation-driven signaling cascade that results in immediate inhibition of Cdk/cyclin complexes to arrest the cell cycle along with recruitment of repair machinery to damaged DNA, followed by a delayed transcriptional response that promotes cell cycle arrest through the induction of Cdk inhibitors, such as p21. In recent years a third layer of complexity has emerged that involves post-transcriptional control of mRNA stability, splicing, and translation as a critical part of the DNA damage response. Here, we describe recent work implicating DNA damage-dependent modification of RNA-binding proteins that are responsible for some of these mRNA effects, highlighting recent work on post-transcriptional regulation of the cell cycle checkpoint protein/apoptosis inducer Gadd45a by the checkpoint kinase MAPKAP Kinase-2.
authors.affiliation: University Hospital Cologne, Center for Internal Medicine, Division of Hematology and Oncology, Cologne, Germany. christian.reinhardt@uk-koeln.de
authors.forename: H Christian
authors.initials: HC
authors.lastname: Reinhardt
authors.forename: Ian G
authors.initials: IG
authors.lastname: Cannell
authors.forename: Sandra
authors.initials: S
authors.lastname: Morandell
authors.forename: Michael B
authors.initials: MB
authors.lastname: Yaffe
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000235:genetics*; D006801:Humans; D014176:Protein Biosynthesis / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D012333:RNA, Messenger