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...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3894167?pdf=render |
| _version_ | 1811296275692257280 |
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| author | Mireille Bétermier Pascale Bertrand Bernard S Lopez |
| author_facet | Mireille Bétermier Pascale Bertrand Bernard S Lopez |
| author_sort | Mireille Bétermier |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T05:46:13Z |
| format | Article |
| id | doaj.art-acb394d704564a60aff25ca1f880157c |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-13T05:46:13Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-acb394d704564a60aff25ca1f880157c2022-12-22T02:59:57ZengPublic 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 |
| spellingShingle | Mireille Bétermier Pascale Bertrand Bernard S Lopez Is non-homologous end-joining really an inherently error-prone process? PLoS Genetics |
| title | 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_short | Is non-homologous end-joining really an inherently error-prone process? |
| title_sort | is non homologous end joining really an inherently error prone process |
| url | http://europepmc.org/articles/PMC3894167?pdf=render |
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