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“An End to a Means”: How DNA-End Structure Shapes the Double-Strand Break Repair Process

Endogenously-arising DNA double-strand breaks (DSBs) rarely harbor canonical 5′-phosphate, 3′-hydroxyl moieties at the ends, which are, regardless of the pathway used, ultimately required for their repair. Cells are therefore endowed with a wide variety of enzymes that can deal with these chemical a...

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Autores principales: Serrano-Benítez, Almudena, Cortés-Ledesma, Felipe, Ruiz, Jose F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965357/
https://www.ncbi.nlm.nih.gov/pubmed/31998749
http://dx.doi.org/10.3389/fmolb.2019.00153
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author Serrano-Benítez, Almudena
Cortés-Ledesma, Felipe
Ruiz, Jose F.
author_facet Serrano-Benítez, Almudena
Cortés-Ledesma, Felipe
Ruiz, Jose F.
author_sort Serrano-Benítez, Almudena
collection PubMed
description Endogenously-arising DNA double-strand breaks (DSBs) rarely harbor canonical 5′-phosphate, 3′-hydroxyl moieties at the ends, which are, regardless of the pathway used, ultimately required for their repair. Cells are therefore endowed with a wide variety of enzymes that can deal with these chemical and structural variations and guarantee the formation of ligatable termini. An important distinction is whether the ends are directly “unblocked” by specific enzymatic activities without affecting the integrity of the DNA molecule and its sequence, or whether they are “processed” by unspecific nucleases that remove nucleotides from the termini. DNA end structure and configuration, therefore, shape the repair process, its requirements, and, importantly, its final outcome. Thus, the molecular mechanisms that coordinate and integrate the cellular response to blocked DSBs, although still largely unexplored, can be particularly relevant for maintaining genome integrity and avoiding malignant transformation and cancer.
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spelling pubmed-69653572020-01-29 “An End to a Means”: How DNA-End Structure Shapes the Double-Strand Break Repair Process Serrano-Benítez, Almudena Cortés-Ledesma, Felipe Ruiz, Jose F. Front Mol Biosci Molecular Biosciences Endogenously-arising DNA double-strand breaks (DSBs) rarely harbor canonical 5′-phosphate, 3′-hydroxyl moieties at the ends, which are, regardless of the pathway used, ultimately required for their repair. Cells are therefore endowed with a wide variety of enzymes that can deal with these chemical and structural variations and guarantee the formation of ligatable termini. An important distinction is whether the ends are directly “unblocked” by specific enzymatic activities without affecting the integrity of the DNA molecule and its sequence, or whether they are “processed” by unspecific nucleases that remove nucleotides from the termini. DNA end structure and configuration, therefore, shape the repair process, its requirements, and, importantly, its final outcome. Thus, the molecular mechanisms that coordinate and integrate the cellular response to blocked DSBs, although still largely unexplored, can be particularly relevant for maintaining genome integrity and avoiding malignant transformation and cancer. Frontiers Media S.A. 2020-01-10 /pmc/articles/PMC6965357/ /pubmed/31998749 http://dx.doi.org/10.3389/fmolb.2019.00153 Text en Copyright © 2020 Serrano-Benítez, Cortés-Ledesma and Ruiz. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Serrano-Benítez, Almudena
Cortés-Ledesma, Felipe
Ruiz, Jose F.
“An End to a Means”: How DNA-End Structure Shapes the Double-Strand Break Repair Process
title “An End to a Means”: How DNA-End Structure Shapes the Double-Strand Break Repair Process
title_full “An End to a Means”: How DNA-End Structure Shapes the Double-Strand Break Repair Process
title_fullStr “An End to a Means”: How DNA-End Structure Shapes the Double-Strand Break Repair Process
title_full_unstemmed “An End to a Means”: How DNA-End Structure Shapes the Double-Strand Break Repair Process
title_short “An End to a Means”: How DNA-End Structure Shapes the Double-Strand Break Repair Process
title_sort “an end to a means”: how dna-end structure shapes the double-strand break repair process
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965357/
https://www.ncbi.nlm.nih.gov/pubmed/31998749
http://dx.doi.org/10.3389/fmolb.2019.00153
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