Abstract
Maintaining the stability of the genome is essential for all organisms, and it is not surprising that damage to DNA has been proposed as an explanation for multiple chronic diseases.1-5 Conserving a pristine genome is therefore of central importance to our health. To overcome the genotoxic stress that occurs as part of daily living, several DNA-repair pathways have evolved. In general, DNA repair is organized within intricate enzymatic networks that deal with particular chemical reactions involving DNA.6,7 Most DNA-repair pathways are characterized by three steps: detection of the DNA modification (or modifications), removal or further modification of the damaged DNA, and resynthesis of the missing nucleotides and ligation of DNA strands. The majority of DNA-repair pathways are highly conserved from bacteria to humans, and inherited defects in DNA repair have been identified as the underlying cause of a growing number of human diseases. Notably, many of these monogenic DNA-repair disorders display features of accelerated aging, supporting the notion that genome maintenance is a key factor for organismal longevity. This review focuses on the physiological consequences of loss of DNA repair, particularly in the context of monogenic DNA-repair diseases.
| Original language | English |
|---|---|
| Journal | New England Journal of Medicine |
| Volume | 377 |
| Issue number | 19 |
| Pages (from-to) | 1868-1876 |
| Number of pages | 9 |
| ISSN | 0028-4793 |
| DOIs | |
| Publication status | Published - Nov 2017 |
