Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and Worms
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-08-01
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| Series: | Biomolecules |
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| Online Access: | http://www.mdpi.com/2218-273X/5/3/1855 |
| _version_ | 1811314554707116032 |
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| author | Diletta Edifizi Björn Schumacher |
| author_facet | Diletta Edifizi Björn Schumacher |
| author_sort | Diletta Edifizi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T11:13:39Z |
| format | Article |
| id | doaj.art-b7632b0bd0f143cca9922b29bb79ef62 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-04-13T11:13:39Z |
| publishDate | 2015-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-b7632b0bd0f143cca9922b29bb79ef622022-12-22T02:49:02ZengMDPI AGBiomolecules2218-273X2015-08-01531855186910.3390/biom5031855biom5031855Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and WormsDiletta Edifizi0Björn Schumacher1Institute for Genome Stability in Aging and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, Cologne 50931, GermanyInstitute for Genome Stability in Aging and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, Cologne 50931, GermanyDNA 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.http://www.mdpi.com/2218-273X/5/3/1855Ultraviolet Light (UV)DNA damageagingNucleotide-excision repair (NER)Global-genome nucleotide-excision repair (GG-NER)Transcription-coupled nucleotide excision repair (TC-NER)Cockayne syndrome (CS)somatotropic axisgrowth hormone/insulin-like growth factor 1 (GH/IGF1) signalinglongevity |
| spellingShingle | Diletta Edifizi Björn Schumacher Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and Worms Biomolecules 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 |
| title | Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and Worms |
| title_full | Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and Worms |
| title_fullStr | Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and Worms |
| title_full_unstemmed | Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and Worms |
| title_short | Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and Worms |
| title_sort | genome instability in development and aging insights from nucleotide excision repair in humans mice and worms |
| topic | 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 |
| url | http://www.mdpi.com/2218-273X/5/3/1855 |
| work_keys_str_mv | AT dilettaedifizi genomeinstabilityindevelopmentandaginginsightsfromnucleotideexcisionrepairinhumansmiceandworms AT bjornschumacher genomeinstabilityindevelopmentandaginginsightsfromnucleotideexcisionrepairinhumansmiceandworms |