Exploring the roles of the SMC5/6 complex in cancer, ageing and kidney disorders

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 02-06-2017

Detalles Bibliográficos
Autor: Schiavoni, Federica
Tipo de recurso: tesis doctoral
Fecha de publicación:2017
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/680791
Acceso en línea:http://hdl.handle.net/10486/680791
Access Level:acceso abierto
Palabra clave:Oncogenes - Tesis doctorales
Enfermedades neurodegenerativas - Aspectos genéticos - Tesis doctorales
Riñones - Enfermedades - Aspectos genéticos - Tesis doctorales
Biología y Biomedicina / Biología
id ES_bfc28c7b5bbc86c9101202ffd74d404a
oai_identifier_str oai:repositorio.uam.es:10486/680791
network_acronym_str ES
network_name_str España
repository_id_str
spelling Exploring the roles of the SMC5/6 complex in cancer, ageing and kidney disordersSchiavoni, FedericaOncogenes - Tesis doctoralesEnfermedades neurodegenerativas - Aspectos genéticos - Tesis doctoralesRiñones - Enfermedades - Aspectos genéticos - Tesis doctoralesBiología y Biomedicina / BiologíaTesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 02-06-2017Esta tesis tiene embargado el acceso al texto completo hasta el 02-12-2018The SMC5/6 complex is part of the Structural Maintenance of Chromosomes (SMC) family of proteins, which includes condensin and cohesin and whose main function is the regulation of chromosomal architecture and organization. While it is known that SMC5/6 participates in genome maintenance, how and where the complex operates remains unclear. With the use of mouse models our work has revealed that NSMCE2, a SUMO ligase that is an integral member of the SMC5/6 complex, suppresses cancer and ageing in mice independently of its SUMO ligase activity. At the cellular level, NSMCE2 deficiency leads to severe segregation defects and increased recombination rates, which would be consistent with a role of the SMC5/6 complex in the resolution of joint DNA molecules before chromosome segregation. Besides the overall accelerated ageing that occurs when Nsmce2 is deleted in adult animals, we here show that these mice present a distinct phenotype on their kidneys that presents all the hallmarks of Karyomegalic interstitial nephritis (KIN). KIN is a progressive kidney disease that in humans has been linked either to exposure to Ochratoxin A, a Topoisomerase II (TOPOII) inhibitor, or to inherit mutations in FAN1, an endonuclease mainly associated to the repair of interstrand cross-links (ICL). Our data suggests that NSMCE2 deficiency leads to the accumulation of topological problems, which would ultimately lead to polyploidy and be the cause of the karyomegaly. In support of this, NSMCE2 deficiency sensitizes cells to the inhibition of TOPOII, and leads to a number of phenotypes that are observed upon TOPOII inhibition. In summary, we here present the second mutation that can trigger KIN in mammals, and propose that topological problems, rather than deficiencies in ICLs repair, are the actual cause of this disease.Fernandez Capetillo, OscarDepartamento de Biología MolecularFacultad de CienciasCentro Nacional de Investigaciones Oncológicas (CNIO)20172017-06-02doctoral thesishttp://purl.org/coar/resource_type/c_db06NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/10486/680791reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6807912026-06-23T12:46:27Z
dc.title.none.fl_str_mv Exploring the roles of the SMC5/6 complex in cancer, ageing and kidney disorders
title Exploring the roles of the SMC5/6 complex in cancer, ageing and kidney disorders
spellingShingle Exploring the roles of the SMC5/6 complex in cancer, ageing and kidney disorders
Schiavoni, Federica
Oncogenes - Tesis doctorales
Enfermedades neurodegenerativas - Aspectos genéticos - Tesis doctorales
Riñones - Enfermedades - Aspectos genéticos - Tesis doctorales
Biología y Biomedicina / Biología
title_short Exploring the roles of the SMC5/6 complex in cancer, ageing and kidney disorders
title_full Exploring the roles of the SMC5/6 complex in cancer, ageing and kidney disorders
title_fullStr Exploring the roles of the SMC5/6 complex in cancer, ageing and kidney disorders
title_full_unstemmed Exploring the roles of the SMC5/6 complex in cancer, ageing and kidney disorders
title_sort Exploring the roles of the SMC5/6 complex in cancer, ageing and kidney disorders
dc.creator.none.fl_str_mv Schiavoni, Federica
author Schiavoni, Federica
author_facet Schiavoni, Federica
author_role author
dc.contributor.none.fl_str_mv Fernandez Capetillo, Oscar
Departamento de Biología Molecular
Facultad de Ciencias
Centro Nacional de Investigaciones Oncológicas (CNIO)
dc.subject.none.fl_str_mv Oncogenes - Tesis doctorales
Enfermedades neurodegenerativas - Aspectos genéticos - Tesis doctorales
Riñones - Enfermedades - Aspectos genéticos - Tesis doctorales
Biología y Biomedicina / Biología
topic Oncogenes - Tesis doctorales
Enfermedades neurodegenerativas - Aspectos genéticos - Tesis doctorales
Riñones - Enfermedades - Aspectos genéticos - Tesis doctorales
Biología y Biomedicina / Biología
description Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 02-06-2017
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-06-02
dc.type.none.fl_str_mv doctoral thesis
http://purl.org/coar/resource_type/c_db06
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/680791
url http://hdl.handle.net/10486/680791
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869418419144622080
score 15.301603

Similares en LA Referencia