TY - JOUR

T1 - Monogenic diseases of DNA repair

AU - Keijzers, Guido

AU - Bakula, Daniela

AU - Scheibye-Knudsen, Morten

PY - 2017/11

Y1 - 2017/11

N2 - 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.

AB - 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.

U2 - 10.1056/NEJMra1703366

DO - 10.1056/NEJMra1703366

M3 - Review

C2 - 29117491

AN - SCOPUS:85033363350

VL - 377

SP - 1868

EP - 1876

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 19

ER -