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

Biomolecules

Björn Schumacher¹  Diletta Edifizi¹ 

[1] Institute for Genome Stability in Aging and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, Cologne 50931, Germany;

关键词: 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;   

DOI  :  10.3390/biom5031855

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown