Cargando…

Alternative end-joining mechanisms: a historical perspective

In the presence of functional DNA repair pathways, DNA double-strand breaks (DSBs) are mainly repaired by non-homologous end-joining (NHEJ) or homologous recombination (HR), two conserved pathways that protect cells from aberrant chromosomal rearrangements. During the past two decades however, unusu...

Descripción completa

Detalles Bibliográficos
Autor principal: Decottignies, Anabelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613618/
https://www.ncbi.nlm.nih.gov/pubmed/23565119
http://dx.doi.org/10.3389/fgene.2013.00048
_version_ 1782264749017268224
author Decottignies, Anabelle
author_facet Decottignies, Anabelle
author_sort Decottignies, Anabelle
collection PubMed
description In the presence of functional DNA repair pathways, DNA double-strand breaks (DSBs) are mainly repaired by non-homologous end-joining (NHEJ) or homologous recombination (HR), two conserved pathways that protect cells from aberrant chromosomal rearrangements. During the past two decades however, unusual and presumably distinct DNA end-joining repair activities have been unraveled in NHEJ-deficient cells and these are likely to operate in various chromosomal contexts and species. Most alternative DNA end-joining events reported so far appear to involve microhomologous sequences and are likely to rely on a subset of HR enzymes, namely those responsible for the single-strand annealing mechanism of HR, and on DNA Ligase III. Usually, microhomologies are not initially present at DSB ends and thus need to be unmasked through DNA end resection, a process that can lead to extensive nucleotide loss and is therefore highly mutagenic. In addition to microhomology-mediated end-joining events, recent studies in mammalian cells point toward the existence of a distinct and still ill defined alternative end-joining pathway that does not appear to rely on pre-existing microhomologies and may possibly involve DNA Ligase I. Whether dependent on microhomologies or not, alternative DNA end-joining mechanisms are likely to be highly mutagenic in vivo, being able to drive telomere fusion events and cancer-associated chromosomal translocations in mouse models. In the future, it will be important to better characterize the genetic requirements of these mutagenic alternative mechanisms of DNA end-joining.
format Online
Article
Text
id pubmed-3613618
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-36136182013-04-05 Alternative end-joining mechanisms: a historical perspective Decottignies, Anabelle Front Genet Oncology In the presence of functional DNA repair pathways, DNA double-strand breaks (DSBs) are mainly repaired by non-homologous end-joining (NHEJ) or homologous recombination (HR), two conserved pathways that protect cells from aberrant chromosomal rearrangements. During the past two decades however, unusual and presumably distinct DNA end-joining repair activities have been unraveled in NHEJ-deficient cells and these are likely to operate in various chromosomal contexts and species. Most alternative DNA end-joining events reported so far appear to involve microhomologous sequences and are likely to rely on a subset of HR enzymes, namely those responsible for the single-strand annealing mechanism of HR, and on DNA Ligase III. Usually, microhomologies are not initially present at DSB ends and thus need to be unmasked through DNA end resection, a process that can lead to extensive nucleotide loss and is therefore highly mutagenic. In addition to microhomology-mediated end-joining events, recent studies in mammalian cells point toward the existence of a distinct and still ill defined alternative end-joining pathway that does not appear to rely on pre-existing microhomologies and may possibly involve DNA Ligase I. Whether dependent on microhomologies or not, alternative DNA end-joining mechanisms are likely to be highly mutagenic in vivo, being able to drive telomere fusion events and cancer-associated chromosomal translocations in mouse models. In the future, it will be important to better characterize the genetic requirements of these mutagenic alternative mechanisms of DNA end-joining. Frontiers Media S.A. 2013-04-02 /pmc/articles/PMC3613618/ /pubmed/23565119 http://dx.doi.org/10.3389/fgene.2013.00048 Text en Copyright © Decottignies. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
spellingShingle Oncology
Decottignies, Anabelle
Alternative end-joining mechanisms: a historical perspective
title Alternative end-joining mechanisms: a historical perspective
title_full Alternative end-joining mechanisms: a historical perspective
title_fullStr Alternative end-joining mechanisms: a historical perspective
title_full_unstemmed Alternative end-joining mechanisms: a historical perspective
title_short Alternative end-joining mechanisms: a historical perspective
title_sort alternative end-joining mechanisms: a historical perspective
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613618/
https://www.ncbi.nlm.nih.gov/pubmed/23565119
http://dx.doi.org/10.3389/fgene.2013.00048
work_keys_str_mv AT decottigniesanabelle alternativeendjoiningmechanismsahistoricalperspective