Is non-homologous end-joining really an inherently error-prone process?
DNA double-strand breaks (DSBs) are harmful lesions leading to genomic instability or diversity. Non-homologous end-joining (NHEJ) is a prominent DSB repair pathway, which has long been considered to be error-prone. However, recent data have pointed to the intrinsic precision of NHEJ. Three reasons can account for the apparent fallibility of NHEJ: 1) the existence of a highly error-prone alternative end-joining process; 2) the adaptability of canonical C-NHEJ (Ku- and Xrcc4/ligase IV-dependent) to imperfect complementary ends; and 3) the requirement to first process chemically incompatible DNA ends that cannot be ligated directly. Thus, C-NHEJ is conservative but adaptable, and the accuracy of the repair is dictated by the structure of the DNA ends rather than by the C-NHEJ machinery. We present data from different organisms that describe the conservative/versatile properties of C-NHEJ. The advantages of the adaptability/versatility of C-NHEJ are discussed for the development of the immune repertoire and the resistance to ionizing radiation, especially at low doses, and for targeted genome manipulation.
CNRS, Centre de Génétique Moléculaire, UPR3404, Gif-sur-Yvette, France ; CNRS, Centre de Recherches de Gif-sur-Yvette, FRC3115, Gif-sur-Yvette, France ; Université Paris-Sud, Département de Biologie, Orsay, France.
Mireille
M
Bétermier
CEA, DSV, Institut de Radiobiologie Moléculaire et Cellulaire, Laboratoire Réparation et Vieillissement, Fontenay-aux-Roses, France ; UMR 8200 CNRS, Villejuif, France.
Pascale
P
Bertrand
Université Paris-Sud, Département de Biologie, Orsay, France ; UMR 8200 CNRS, Villejuif, France ; Institut de Cancérologie, Gustave Roussy, Villejuif, France.
Bernard S
BS
Lopez
D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004249:DNA Damage / Q000276:immunology / Q000528:radiation effects; D059766:DNA End-Joining Repair / Q000235:genetics* / Q000276:immunology; D011088:DNA Ligases; D004260:DNA Repair / Q000235:genetics* / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology; D042822:Genomic Instability; D011839:Radiation, Ionizing; D011995:Recombination, Genetic / Q000276:immunology
D004268:DNA-Binding Proteins; C101467:XRCC4 protein, human; D011088:DNA Ligases