Next Article in Journal
Oxidative Stress and Maxi Calcium-Activated Potassium (BK) Channels
Next Article in Special Issue
Targeting the Checkpoint to Kill Cancer Cells
Previous Article in Journal
Complementary LC-MS/MS-Based N-Glycan, N-Glycopeptide, and Intact N-Glycoprotein Profiling Reveals Unconventional Asn71-Glycosylation of Human Neutrophil Cathepsin G
Previous Article in Special Issue
Bacterial Genotoxins: Merging the DNA Damage Response into Infection Biology
Article Menu

Export Article

Open AccessReview
Biomolecules 2015, 5(3), 1855-1869; doi:10.3390/biom5031855

Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and Worms

1
Institute for Genome Stability in Aging and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, Cologne 50931, Germany
2
Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), Center for Molecular Medicine Cologne (CMMC) and Systems Biology of Aging Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, Cologne 50931, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Wolf-Dietrich Heyer, Thomas Helleday and Fumio Hanaoka
Received: 16 July 2015 / Revised: 6 August 2015 / Accepted: 7 August 2015 / Published: 13 August 2015
(This article belongs to the Special Issue DNA Damage Response)
View Full-Text   |   Download PDF [12295 KB, uploaded 28 August 2015]   |  

Abstract

DNA damage causally contributes to aging and cancer. Congenital defects in nucleotide excision repair (NER) lead to distinct cancer-prone and premature aging syndromes. The genetics of NER mutations have provided important insights into the distinct consequences of genome instability. Recent work in mice and C. elegans has shed new light on the mechanisms through which developing and aging animals respond to persistent DNA damage. The various NER mouse mutants have served as important disease models for Xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD), while the traceable genetics of C. elegans have allowed the mechanistic delineation of the distinct outcomes of genome instability in metazoan development and aging. Intriguingly, highly conserved longevity assurance mechanisms respond to transcription-blocking DNA lesions in mammals as well as in worms and counteract the detrimental consequences of persistent DNA damage. The insulin-like growth factor signaling (IIS) effector transcription factor DAF-16 could indeed overcome DNA damage-driven developmental growth delay and functional deterioration even when DNA damage persists. Longevity assurance mechanisms might thus delay DNA damage-driven aging by raising the threshold when accumulating DNA damage becomes detrimental for physiological tissue functioning. View Full-Text
Keywords: Ultraviolet Light (UV); DNA damage; aging; Nucleotide-excision repair (NER); Global-genome nucleotide-excision repair (GG-NER); Transcription-coupled nucleotide excision repair (TC-NER); Cockayne syndrome (CS); somatotropic axis; growth hormone/insulin-like growth factor 1 (GH/IGF1) signaling; longevity Ultraviolet Light (UV); DNA damage; aging; Nucleotide-excision repair (NER); Global-genome nucleotide-excision repair (GG-NER); Transcription-coupled nucleotide excision repair (TC-NER); Cockayne syndrome (CS); somatotropic axis; growth hormone/insulin-like growth factor 1 (GH/IGF1) signaling; longevity
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Edifizi, D.; Schumacher, B. Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and Worms. Biomolecules 2015, 5, 1855-1869.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biomolecules EISSN 2218-273X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top