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Controlling DNA-end resection: a new task for CDKs

DNA double-strand breaks (DSBs) are repaired by two major pathways: homologous recombination (HR) and non-homologous end-joining (NHEJ). The choice between HR and NHEJ is highly regulated during the cell cycle. DNA-end resection, an evolutionarily conserved process that generates long stretches of s...

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Autores principales: Ferretti, Lorenza P., Lafranchi, Lorenzo, Sartori, Alessandro A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669801/
https://www.ncbi.nlm.nih.gov/pubmed/23760669
http://dx.doi.org/10.3389/fgene.2013.00099
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author Ferretti, Lorenza P.
Lafranchi, Lorenzo
Sartori, Alessandro A.
author_facet Ferretti, Lorenza P.
Lafranchi, Lorenzo
Sartori, Alessandro A.
author_sort Ferretti, Lorenza P.
collection PubMed
description DNA double-strand breaks (DSBs) are repaired by two major pathways: homologous recombination (HR) and non-homologous end-joining (NHEJ). The choice between HR and NHEJ is highly regulated during the cell cycle. DNA-end resection, an evolutionarily conserved process that generates long stretches of single-stranded DNA, plays a critical role in pathway choice, as it commits cells to HR, while, at the same time, suppressing NHEJ. As erroneous DSB repair is a major source of genomic instability-driven tumorigenesis, DNA-end resection factors, and in particular their regulation by post-translational modifications, have become the subject of extensive research over the past few years. Recent work has implicated phosphorylation at S/T-P motifs by cyclin-dependent kinases (CDKs) as a major regulatory mechanism of DSB repair. Intriguingly, CDK activity was found to be critically important for the coordinated and timely execution of DNA-end resection, and key players in this process were subsequently identified as CDK substrates. In this mini review, we provide an overview of the current understanding of how the DNA-end resection machinery in yeast and human cells is controlled by CDK-mediated phosphorylation.
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spelling pubmed-36698012013-06-11 Controlling DNA-end resection: a new task for CDKs Ferretti, Lorenza P. Lafranchi, Lorenzo Sartori, Alessandro A. Front Genet Oncology DNA double-strand breaks (DSBs) are repaired by two major pathways: homologous recombination (HR) and non-homologous end-joining (NHEJ). The choice between HR and NHEJ is highly regulated during the cell cycle. DNA-end resection, an evolutionarily conserved process that generates long stretches of single-stranded DNA, plays a critical role in pathway choice, as it commits cells to HR, while, at the same time, suppressing NHEJ. As erroneous DSB repair is a major source of genomic instability-driven tumorigenesis, DNA-end resection factors, and in particular their regulation by post-translational modifications, have become the subject of extensive research over the past few years. Recent work has implicated phosphorylation at S/T-P motifs by cyclin-dependent kinases (CDKs) as a major regulatory mechanism of DSB repair. Intriguingly, CDK activity was found to be critically important for the coordinated and timely execution of DNA-end resection, and key players in this process were subsequently identified as CDK substrates. In this mini review, we provide an overview of the current understanding of how the DNA-end resection machinery in yeast and human cells is controlled by CDK-mediated phosphorylation. Frontiers Media S.A. 2013-06-03 /pmc/articles/PMC3669801/ /pubmed/23760669 http://dx.doi.org/10.3389/fgene.2013.00099 Text en Copyright © 2013 Ferretti, Lafranchi and Sartori. 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
Ferretti, Lorenza P.
Lafranchi, Lorenzo
Sartori, Alessandro A.
Controlling DNA-end resection: a new task for CDKs
title Controlling DNA-end resection: a new task for CDKs
title_full Controlling DNA-end resection: a new task for CDKs
title_fullStr Controlling DNA-end resection: a new task for CDKs
title_full_unstemmed Controlling DNA-end resection: a new task for CDKs
title_short Controlling DNA-end resection: a new task for CDKs
title_sort controlling dna-end resection: a new task for cdks
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669801/
https://www.ncbi.nlm.nih.gov/pubmed/23760669
http://dx.doi.org/10.3389/fgene.2013.00099
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