title: Posttranscriptional regulation of gene expression-adding another layer of complexity to the DNA damage response.
abstract: In response to DNA damage, cells activate a complex, kinase-based signaling network to arrest the cell cycle and allow time for DNA repair, or, if the extend of damage is beyond repair capacity, induce apoptosis. This signaling network, which is collectively referred to as the DNA damage response (DDR), is primarily thought to consist of two components-a rapid phosphorylation-driven signaling cascade that results in immediate inhibition of Cdk/cyclin complexes and a delayed transcriptional response that promotes a prolonged cell cycle arrest through the induction of Cdk inhibitors, such as p21. In recent years a third layer of complexity has emerged that involves potent posttranscriptional regulatory mechanisms that control the cellular response to DNA damage. Although much has been written on the relevance of the DDR in cancer and on the post-transcriptional role of microRNAs (miRs) in cancer, the post-transcriptional regulation of the DDR by non-coding RNAs and RNA-binding proteins (RBPs) still remains elusive in large parts. Here, we review the recent developments in this exciting new area of research in the cellular response to genotoxic stress. We put specific emphasis on the role of RBPs and the control of their function through DNA damage-activated protein kinases.
authors.affiliation: Division of Hematology and Oncology, Center for Internal Medicine, University Hospital of Cologne Cologne, Germany.
authors.forename: Jorge
authors.initials: J
authors.lastname: Boucas
authors.forename: Arina
authors.initials: A
authors.lastname: Riabinska
authors.forename: Mladen
authors.initials: M
authors.lastname: Jokic
authors.forename: Grit S
authors.initials: GS
authors.lastname: Herter-Sprie
authors.forename: Shuhua
authors.initials: S
authors.lastname: Chen
authors.forename: Katja
authors.initials: K
authors.lastname: Höpker
authors.forename: H Christian
authors.initials: HC
authors.lastname: Reinhardt