Universität zu Köln

Edifizi, Diletta (2017). A multidimensional omics analysis of the DNA damage response in Caenorhabditis elegans. PhD thesis, Universität zu Köln.

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Abstract

DNA damage comprises a causal factor for ageing and ageing-associated diseases. Defects in genome maintenance pathways give rise to a variety of human congenital syndromes that are characterized by growth retardation, cancer susceptibility, and accelerated ageing. The specific consequences of unrepaired DNA damage in human diseases are particularly apparent in syndromes caused by distinct nucleotide excision repair (NER) defects; however, with yet poorly understood genotype-phenotype correlations and highly complex disease phenotypes. It is established that the equivalent mutations in the simple metazoan Caenorhabditis elegans reflect the distinct outcomes of DNA repair defects and allow investigation of the consequences of persistent DNA damage during animal development and ageing. Here, we conducted proteome, lipidome, and phosphoproteome analysis of NER-deficient animals in response to UV-B treatment to gain comprehensive insights into the full range of physiological adaptations to unrepaired DNA damage. We derive metabolic changes indicative of a tissue maintenance program and implicate an autophagy-mediated protoestatic response. We assign central roles for the IIS regulator DAF-2, and the EGF- and AMPK-like signalling pathways in orchestrating the adaptive response to DNA damage. Our results provide new insights into the DNA damage responses in the organismal context.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Edifizi, Diletta didyedi@gmail.com UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-79223
Date:	29 August 2017
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	Natural sciences and mathematics Life sciences
Uncontrolled Keywords:	Keywords Language DNA damage English aging English protein homeostasis UNSPECIFIED
Date of oral exam:	30 May 2017
Referee:	Name Academic Title Schumacher, Björn Prof.Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/7922