Universität zu Köln

Brinkmann, Kerstin, Schell, Michael, Hoppe, Thorsten ORCID: 0000-0002-4734-9352 and Kashkar, Hamid (2015). Regulation of the DNA damage response by ubiquitin conjugation. Front. Genet., 6. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-8021

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Brinkmann, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Schell, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoppe, Thorsten UNSPECIFIED orcid.org/0000-0002-4734-9352 UNSPECIFIED Kashkar, Hamid UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-409903
DOI:	10.3389/fgene.2015.00098
Journal or Publication Title:	Front. Genet.
Volume:	6
Date:	2015
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-8021
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language STRAND-BREAK REPAIR; PROTEASOME-DEPENDENT DEGRADATION; P53-INDUCED RING-H2 PROTEIN; SMALL-MOLECULE ANTAGONISTS; MDM2 GENE AMPLIFICATION; E3 LIGASE; TUMOR-SUPPRESSOR; POOR-PROGNOSIS; EPIGENETIC INACTIVATION; INDUCED APOPTOSIS Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/40990