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...
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doaj-acb394d704564a60aff25ca1f880157c2020-11-24T21:32:38ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-01-01101e100408610.1371/journal.pgen.1004086Is non-homologous end-joining really an inherently error-prone process?Mireille BétermierPascale BertrandBernard S LopezDNA 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.http://europepmc.org/articles/PMC3894167?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mireille Bétermier Pascale Bertrand Bernard S Lopez |
spellingShingle |
Mireille Bétermier Pascale Bertrand Bernard S Lopez Is non-homologous end-joining really an inherently error-prone process? PLoS Genetics |
author_facet |
Mireille Bétermier Pascale Bertrand Bernard S Lopez |
author_sort |
Mireille Bétermier |
title |
Is non-homologous end-joining really an inherently error-prone process? |
title_short |
Is non-homologous end-joining really an inherently error-prone process? |
title_full |
Is non-homologous end-joining really an inherently error-prone process? |
title_fullStr |
Is non-homologous end-joining really an inherently error-prone process? |
title_full_unstemmed |
Is non-homologous end-joining really an inherently error-prone process? |
title_sort |
is non-homologous end-joining really an inherently error-prone process? |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3894167?pdf=render |
work_keys_str_mv |
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