CDK-mediated phosphorylation of Yku80 and its role in DNA repair

DNA double-strand breaks (DSBs) are considered the most deleterious lesions of DNA and they are repaired by means of two main mechanisms: homologous recombination (HR) and non-homologous endjoining (NHEJ). These mechanisms are regulated throughout the cell cycle being HR restricted to the S/G2 phase...

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Detalles Bibliográficos
Autor: Carballar Ruiz, María de los Reyes
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/671096
Acceso en línea:http://hdl.handle.net/10803/671096
Access Level:acceso abierto
Palabra clave:Yku80
Ku80
NHEJ
HR
DNA Repair
CDK
Cell cycle
Ciencias de la salud
61
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spelling CDK-mediated phosphorylation of Yku80 and its role in DNA repairCarballar Ruiz, María de los ReyesYku80Ku80NHEJHRDNA RepairCDKCell cycleCiencias de la salud61DNA double-strand breaks (DSBs) are considered the most deleterious lesions of DNA and they are repaired by means of two main mechanisms: homologous recombination (HR) and non-homologous endjoining (NHEJ). These mechanisms are regulated throughout the cell cycle being HR restricted to the S/G2 phases while NHEJ is active during the different phases of the cell cycle. Here I presented evidence of NHEJ regulation by CDK phosphorylation of one of the key proteins of the NHEJ repair pathway, Yku80. Yku80 is phosphorylated both in vitro and in vivo by the CDK Pho85 in association with the G1 cyclin Pcl1. A non-phosphorylatable version of Yku80 (yku80-S623A) shows increased NHEJ activity, reduced HR events and higher sensitivity upon bleomycin treatment, a DSB-inducing agent, specifically when DNA damage was induced during the G2 phase of the cell cycle. Interestingly, the overexpression of the nonphosphorylatable version of human Ku80 (Ku80T629A) increased bleomycin sensitivity in different cancer linessuggesting Ku80 phosphorylation and its role in DSB repair regulation might be conserved. Thus, the results presented in this work provide evidence of a new mechanism to regulate DSB repair pathway choice by CDK-mediated phosphorylation of Yku80.Universitat Internacional de CatalunyaJiménez Jiménez, JavierBru Rullo, SamuelUniversitat Internacional de Catalunya. Departament de Ciències Bàsiques202120212021info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion278 p.application/pdfapplication/pdfhttp://hdl.handle.net/10803/671096TDX (Tesis Doctorals en Xarxa)reponame:TDR. Tesis Doctorales en Redinstname:CBUC, CESCAInglésL'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by-nc-nd/4.0/http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:www.tdx.cat:10803/6710962026-06-14T12:46:07Z
dc.title.none.fl_str_mv CDK-mediated phosphorylation of Yku80 and its role in DNA repair
title CDK-mediated phosphorylation of Yku80 and its role in DNA repair
spellingShingle CDK-mediated phosphorylation of Yku80 and its role in DNA repair
Carballar Ruiz, María de los Reyes
Yku80
Ku80
NHEJ
HR
DNA Repair
CDK
Cell cycle
Ciencias de la salud
61
title_short CDK-mediated phosphorylation of Yku80 and its role in DNA repair
title_full CDK-mediated phosphorylation of Yku80 and its role in DNA repair
title_fullStr CDK-mediated phosphorylation of Yku80 and its role in DNA repair
title_full_unstemmed CDK-mediated phosphorylation of Yku80 and its role in DNA repair
title_sort CDK-mediated phosphorylation of Yku80 and its role in DNA repair
dc.creator.none.fl_str_mv Carballar Ruiz, María de los Reyes
author Carballar Ruiz, María de los Reyes
author_facet Carballar Ruiz, María de los Reyes
author_role author
dc.contributor.none.fl_str_mv Jiménez Jiménez, Javier
Bru Rullo, Samuel
Universitat Internacional de Catalunya. Departament de Ciències Bàsiques
dc.subject.none.fl_str_mv Yku80
Ku80
NHEJ
HR
DNA Repair
CDK
Cell cycle
Ciencias de la salud
61
topic Yku80
Ku80
NHEJ
HR
DNA Repair
CDK
Cell cycle
Ciencias de la salud
61
description DNA double-strand breaks (DSBs) are considered the most deleterious lesions of DNA and they are repaired by means of two main mechanisms: homologous recombination (HR) and non-homologous endjoining (NHEJ). These mechanisms are regulated throughout the cell cycle being HR restricted to the S/G2 phases while NHEJ is active during the different phases of the cell cycle. Here I presented evidence of NHEJ regulation by CDK phosphorylation of one of the key proteins of the NHEJ repair pathway, Yku80. Yku80 is phosphorylated both in vitro and in vivo by the CDK Pho85 in association with the G1 cyclin Pcl1. A non-phosphorylatable version of Yku80 (yku80-S623A) shows increased NHEJ activity, reduced HR events and higher sensitivity upon bleomycin treatment, a DSB-inducing agent, specifically when DNA damage was induced during the G2 phase of the cell cycle. Interestingly, the overexpression of the nonphosphorylatable version of human Ku80 (Ku80T629A) increased bleomycin sensitivity in different cancer linessuggesting Ku80 phosphorylation and its role in DSB repair regulation might be conserved. Thus, the results presented in this work provide evidence of a new mechanism to regulate DSB repair pathway choice by CDK-mediated phosphorylation of Yku80.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10803/671096
url http://hdl.handle.net/10803/671096
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 278 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Universitat Internacional de Catalunya
publisher.none.fl_str_mv Universitat Internacional de Catalunya
dc.source.none.fl_str_mv TDX (Tesis Doctorals en Xarxa)
reponame:TDR. Tesis Doctorales en Red
instname:CBUC, CESCA
instname_str CBUC, CESCA
reponame_str TDR. Tesis Doctorales en Red
collection TDR. Tesis Doctorales en Red
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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