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. © 2014 bétermier et al.