title: Regulation of the DNA damage response by ubiquitin conjugation.
abstract: In response to DNA damage, cells activate a highly conserved and complex kinase-based signaling network, commonly referred to as the DNA damage response (DDR), to safeguard genomic integrity. The DDR consists of a set of tightly regulated events, including detection of DNA damage, accumulation of DNA repair factors at the site of damage, and finally physical repair of the lesion. Upon overwhelming damage the DDR provokes detrimental cellular actions by involving the apoptotic machinery and inducing a coordinated demise of the damaged cells (DNA damage-induced apoptosis, DDIA). These diverse actions involve transcriptional activation of several genes that govern the DDR. Moreover, recent observations highlighted the role of ubiquitylation in orchestrating the DDR, providing a dynamic cellular regulatory circuit helping to guarantee genomic stability and cellular homeostasis (Popovic et al., 2014). One of the hallmarks of human cancer is genomic instability (Hanahan and Weinberg, 2011). Not surprisingly, deregulation of the DDR can lead to human diseases, including cancer, and can induce resistance to genotoxic anti-cancer therapy (Lord and Ashworth, 2012). Here, we summarize the role of ubiquitin-signaling in the DDR with special emphasis on its role in cancer and highlight the therapeutic value of the ubiquitin-conjugation machinery as a target in anti-cancer treatment strategy.
authors: Centre for Molecular Medicine Cologne and Institute for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne Cologne, Germany ; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University Hospital of Cologne Cologne, Germany.
authors: Kerstin
authors: K
authors: Brinkmann
authors: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University Hospital of Cologne Cologne, Germany ; Institute for Genetics, University of Cologne Cologne, Germany.
authors: Michael
authors: M
authors: Schell
authors: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University Hospital of Cologne Cologne, Germany ; Institute for Genetics, University of Cologne Cologne, Germany.
authors: Thorsten
authors: T
authors: Hoppe
authors: Centre for Molecular Medicine Cologne and Institute for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne Cologne, Germany ; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University Hospital of Cologne Cologne, Germany.
authors: Hamid
authors: H
authors: Kashkar
keywords: Bcl-2; DNA damage; apoptosis; genotoxic anti-cancer therapy; p53; ubiquitylation