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

dc.contributor
Universitat Internacional de Catalunya. Departament de Ciències Bàsiques
dc.contributor.author
Carballar Ruiz, María de los Reyes
dc.date.accessioned
2021-03-11T19:33:09Z
dc.date.available
2021-03-11T19:33:09Z
dc.date.issued
2021-02-25
dc.identifier.uri
http://hdl.handle.net/10803/671096
dc.description.abstract
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.
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dc.format.extent
278 p.
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dc.format.mimetype
application/pdf
dc.language.iso
eng
en_US
dc.publisher
Universitat Internacional de Catalunya
dc.rights.license
L'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/
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
*
dc.source
TDX (Tesis Doctorals en Xarxa)
dc.subject
Yku80
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dc.subject
Ku80
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dc.subject
NHEJ
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dc.subject
HR
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dc.subject
DNA Repair
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dc.subject
CDK
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dc.subject
Cell cycle
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dc.subject.other
Ciencias de la salud
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dc.title
CDK-mediated phosphorylation of Yku80 and its role in DNA repair
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dc.type
info:eu-repo/semantics/doctoralThesis
dc.type
info:eu-repo/semantics/publishedVersion
dc.subject.udc
61
en_US
dc.contributor.director
Jiménez Jiménez, Javier
dc.contributor.director
Bru Rullo, Samuel
dc.embargo.terms
cap
en_US
dc.rights.accessLevel
info:eu-repo/semantics/openAccess


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