CDK-mediated phosphorylation of Yku80 and its role in DNA repair
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Author
Carballar Ruiz, María de los Reyes
Other authors
Jiménez Jiménez, Javier
Universitat Internacional de Catalunya. Departament de Ciències Bàsiques
Date of defense
2021-03-11T19:33:09Z2021-03-11T19:33:09Z
2021-02-25
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.
Document Type
Thesis
Published version
Language
English
Subjects and keywords
Yku80
Ku80
NHEJ
HR
DNA Repair
CDK
Cell cycle
Ciencias de la salud
61
Pages
278 p.
application/pdf
application/pdf
Publisher
Universitat Internacional de Catalunya
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Rights
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/