{"id":{"repo_id":"dialnet","oai_identifier":"oai:dialnet.unirioja.es:TES0000023232"},"canonical_url":"https://search.dev.ndltd.org/etd/dialnet/oai:dialnet.unirioja.es:TES0000023232","repository":{"repo_id":"dialnet","name":"Dialnet","base_url":"https://dialnet.unirioja.es/oaites/OAIHandler"},"display":{"title":"Regulation of INTS-6 by post-translational modifications: exploring phosphorylation, SUMOylation and their biological relevance in Caenorhabditis elegans","abstract":"The Integrator complex, initially identified by Baillat et al. in 2005, is an evolutionarily conserved protein complex consisting of at least 15 subunits in Homo sapiens, 14 of which have also been described in Caenorhabditis elegans. Although it was initially thought to play a central role in snRNA processing, additional functions have been described since then in other key processes such as development, DNA damage response, and gene expression regulation. In this context and in line with the group's research efforts, the overall objective of this thesis is to study subunit 6 of the Integrator complex (INTS-6), with a particular focus on its role in pathological contexts, such as tumor development, and on the mechanisms regulating its activity mediated by post-translational modifications. First, we analyzed INTS6 expression and snRNA processing in samples from patients with colorectal cancer, in order to explore its potential diagnostic value in this type of tumor. Next, we focused on the molecular aspects of INTS-6 involvement during the response to DNA damage in C. elegans, with the aim of evaluating whether the mechanism described in humans is conserved in nematodes. Finally, we addressed the regulatory mechanisms of INTS-6, focusing on two post-translational modifications: phosphorylation, as a possible key point in DNA damage repair by homologous recombination, and SUMOylation, which could influence other cellular processes, such as the subcellular localization of the protein or the formation of protein complexes. Finally, this work aims to highlight the relevance of both basic research, which is essential for unraveling processes at the molecular level, and computational tools, which offer complementary approaches when classical techniques prove challenging. Together, these efforts contribute to building a solid knowledge base that facilitates the subsequent translation of results.","abstract_html":"The Integrator complex, initially identified by Baillat et al. in 2005, is an evolutionarily conserved protein complex consisting of at least 15 subunits in Homo sapiens, 14 of which have also been described in Caenorhabditis elegans. Although it was initially thought to play a central role in snRNA processing, additional functions have been described since then in other key processes such as development, DNA damage response, and gene expression regulation. In this context and in line with the group's research efforts, the overall objective of this thesis is to study subunit 6 of the Integrator complex (INTS-6), with a particular focus on its role in pathological contexts, such as tumor development, and on the mechanisms regulating its activity mediated by post-translational modifications. First, we analyzed INTS6 expression and snRNA processing in samples from patients with colorectal cancer, in order to explore its potential diagnostic value in this type of tumor. Next, we focused on the molecular aspects of INTS-6 involvement during the response to DNA damage in C. elegans, with the aim of evaluating whether the mechanism described in humans is conserved in nematodes. Finally, we addressed the regulatory mechanisms of INTS-6, focusing on two post-translational modifications: phosphorylation, as a possible key point in DNA damage repair by homologous recombination, and SUMOylation, which could influence other cellular processes, such as the subcellular localization of the protein or the formation of protein complexes. Finally, this work aims to highlight the relevance of both basic research, which is essential for unraveling processes at the molecular level, and computational tools, which offer complementary approaches when classical techniques prove challenging. Together, these efforts contribute to building a solid knowledge base that facilitates the subsequent translation of results.","abstract_has_math":false,"creators":["Romero Aranda, Cristina"],"institution":"Universidad de La Rioja (España)","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Cabello Pardos, Juan (null)","Gómez Orte, Eva (null)"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2026,"date_issued":"2026","date_published":"2026","updated_at":"2026-07-24T06:27:11Z","subjects":[],"languages":["eng"],"rights":["LICENCIA DE USO: Los documentos a texto completo incluidos en Dialnet son de acceso libre y propiedad de sus autores y/o editores. Por tanto, cualquier acto de reproducción, distribución, comunicación pública y/o transformación total o parcial requiere el consentimiento expreso y escrito de aquéllos. Cualquier enlace al texto completo de estos documentos deberá hacerse a través de la URL oficial de éstos en Dialnet. Más información: https://dialnet.unirioja.es/info/derechosOAI | INTELLECTUAL PROPERTY RIGHTS STATEMENT: Full text documents hosted by Dialnet are protected by copyright and/or related rights. This digital object is accessible without charge, but its use is subject to the licensing conditions set by its authors or editors. Unless expressly stated otherwise in the licensing conditions, you are free to linking, browsing, printing and making a copy for your own personal purposes. All other acts of reproduction and communication to the public are subject to the licensing conditions expressed by editors and authors and require consent from them. Any link to this document should be made using its official URL in Dialnet. More info: https://dialnet.unirioja.es/info/derechosOAI"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dialnet.unirioja.es/servlet/oaites?codigo=399607","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Cabello Pardos, Juan (null)","Gómez Orte, Eva (null)"]},{"key":"dc:creator","label":"Author","values":["Romero Aranda, Cristina"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2026"]},{"key":"dc:publisher","label":"Institution","values":["Universidad de La Rioja (España)"]},{"key":"dc:type","label":"Dc Type","values":["text (thesis)"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["LICENCIA DE USO: Los documentos a texto completo incluidos en Dialnet son de acceso libre y propiedad de sus autores y/o editores. Por tanto, cualquier acto de reproducción, distribución, comunicación pública y/o transformación total o parcial requiere el consentimiento expreso y escrito de aquéllos. Cualquier enlace al texto completo de estos documentos deberá hacerse a través de la URL oficial de éstos en Dialnet. Más información: https://dialnet.unirioja.es/info/derechosOAI | INTELLECTUAL PROPERTY RIGHTS STATEMENT: Full text documents hosted by Dialnet are protected by copyright and/or related rights. This digital object is accessible without charge, but its use is subject to the licensing conditions set by its authors or editors. Unless expressly stated otherwise in the licensing conditions, you are free to linking, browsing, printing and making a copy for your own personal purposes. All other acts of reproduction and communication to the public are subject to the licensing conditions expressed by editors and authors and require consent from them. Any link to this document should be made using its official URL in Dialnet. More info: https://dialnet.unirioja.es/info/derechosOAI"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dialnet.unirioja.es/servlet/oaites?codigo=399607"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The Integrator complex, initially identified by Baillat et al. in 2005, is an evolutionarily conserved protein complex consisting of at least 15 subunits in Homo sapiens, 14 of which have also been described in Caenorhabditis elegans. Although it was initially thought to play a central role in snRNA processing, additional functions have been described since then in other key processes such as development, DNA damage response, and gene expression regulation. In this context and in line with the group's research efforts, the overall objective of this thesis is to study subunit 6 of the Integrator complex (INTS-6), with a particular focus on its role in pathological contexts, such as tumor development, and on the mechanisms regulating its activity mediated by post-translational modifications. First, we analyzed INTS6 expression and snRNA processing in samples from patients with colorectal cancer, in order to explore its potential diagnostic value in this type of tumor. Next, we focused on the molecular aspects of INTS-6 involvement during the response to DNA damage in C. elegans, with the aim of evaluating whether the mechanism described in humans is conserved in nematodes. Finally, we addressed the regulatory mechanisms of INTS-6, focusing on two post-translational modifications: phosphorylation, as a possible key point in DNA damage repair by homologous recombination, and SUMOylation, which could influence other cellular processes, such as the subcellular localization of the protein or the formation of protein complexes. Finally, this work aims to highlight the relevance of both basic research, which is essential for unraveling processes at the molecular level, and computational tools, which offer complementary approaches when classical techniques prove challenging. Together, these efforts contribute to building a solid knowledge base that facilitates the subsequent translation of results.","El complejo Integrador, identificado inicialmente por Baillat et al., en 2005, es un complejo proteico evolutivamente conservado que está formado por al menos 15 subunidades en Homo sapiens, de las cuales 14 también han sido descritas en Caenorhabditis elegans. Aunque inicialmente se le atribuyó un papel central en el procesamiento de snRNAs, posteriormente se han descrito funciones adicionales en procesos clave como el desarrollo, la respuesta al daño en el ADN o la regulación de la expresión génica. En este contexto y en continuidad con las líneas de investigación del grupo, el objetivo general de esta tesis es el estudio de la subunidad 6 del complejo Integrador (INTS-6), con especial interés en su papel en contextos patológicos, como el desarrollo tumoral, y en los mecanismos de regulación de su actividad mediados por modificaciones postraduccionales. En primer lugar, se analizó la expresión de INTS6 y el procesamiento de snRNAs en muestras de pacientes con cáncer colorrectal, con el fin de explorar su posible valor diagnóstico en este tipo de tumores. Posteriormente, nos centramos en los aspectos moleculares de la implicación de INTS-6 en la respuesta a daño en ADN en C. elegans, con el objetivo de evaluar si el mecanismo descrito en humanos se conserva en nematodos. Finalmente, se abordaron los mecanismos de regulación de INTS-6, poniendo el foco en dos modificaciones postraduccionales: la fosforilación, como posible punto clave en la reparación de daños en ADN por recombinación homóloga, y la SUMOilación, que podría influir en otros procesos celulares, como la localización subcelular de la proteína o la formación de complejos proteicos. Por último, este trabajo pretende poner en valor la importancia tanto de la investigación básica, fundamental para desentrañar los procesos a nivel molecular, como de las herramientas computacionales, que ofrecen enfoques complementarios cuando las técnicas clásicas resultan un desafío. En conjunto, estos esfuerzos contribuyen a construir una base de conocimiento sólida que facilite la posterior traslación de los resultados."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Regulation of INTS-6 by post-translational modifications: exploring phosphorylation, SUMOylation and their biological relevance in Caenorhabditis elegans"]}]}],"canonical_facts":{"dc:contributor":["Cabello Pardos, Juan (null)","Gómez Orte, Eva (null)"],"dc:creator":["Romero Aranda, Cristina"],"dc:date":["2026"],"dc:description":["The Integrator complex, initially identified by Baillat et al. in 2005, is an evolutionarily conserved protein complex consisting of at least 15 subunits in Homo sapiens, 14 of which have also been described in Caenorhabditis elegans. Although it was initially thought to play a central role in snRNA processing, additional functions have been described since then in other key processes such as development, DNA damage response, and gene expression regulation. In this context and in line with the group's research efforts, the overall objective of this thesis is to study subunit 6 of the Integrator complex (INTS-6), with a particular focus on its role in pathological contexts, such as tumor development, and on the mechanisms regulating its activity mediated by post-translational modifications. First, we analyzed INTS6 expression and snRNA processing in samples from patients with colorectal cancer, in order to explore its potential diagnostic value in this type of tumor. Next, we focused on the molecular aspects of INTS-6 involvement during the response to DNA damage in C. elegans, with the aim of evaluating whether the mechanism described in humans is conserved in nematodes. Finally, we addressed the regulatory mechanisms of INTS-6, focusing on two post-translational modifications: phosphorylation, as a possible key point in DNA damage repair by homologous recombination, and SUMOylation, which could influence other cellular processes, such as the subcellular localization of the protein or the formation of protein complexes. Finally, this work aims to highlight the relevance of both basic research, which is essential for unraveling processes at the molecular level, and computational tools, which offer complementary approaches when classical techniques prove challenging. Together, these efforts contribute to building a solid knowledge base that facilitates the subsequent translation of results.","El complejo Integrador, identificado inicialmente por Baillat et al., en 2005, es un complejo proteico evolutivamente conservado que está formado por al menos 15 subunidades en Homo sapiens, de las cuales 14 también han sido descritas en Caenorhabditis elegans. Aunque inicialmente se le atribuyó un papel central en el procesamiento de snRNAs, posteriormente se han descrito funciones adicionales en procesos clave como el desarrollo, la respuesta al daño en el ADN o la regulación de la expresión génica. En este contexto y en continuidad con las líneas de investigación del grupo, el objetivo general de esta tesis es el estudio de la subunidad 6 del complejo Integrador (INTS-6), con especial interés en su papel en contextos patológicos, como el desarrollo tumoral, y en los mecanismos de regulación de su actividad mediados por modificaciones postraduccionales. En primer lugar, se analizó la expresión de INTS6 y el procesamiento de snRNAs en muestras de pacientes con cáncer colorrectal, con el fin de explorar su posible valor diagnóstico en este tipo de tumores. Posteriormente, nos centramos en los aspectos moleculares de la implicación de INTS-6 en la respuesta a daño en ADN en C. elegans, con el objetivo de evaluar si el mecanismo descrito en humanos se conserva en nematodos. Finalmente, se abordaron los mecanismos de regulación de INTS-6, poniendo el foco en dos modificaciones postraduccionales: la fosforilación, como posible punto clave en la reparación de daños en ADN por recombinación homóloga, y la SUMOilación, que podría influir en otros procesos celulares, como la localización subcelular de la proteína o la formación de complejos proteicos. Por último, este trabajo pretende poner en valor la importancia tanto de la investigación básica, fundamental para desentrañar los procesos a nivel molecular, como de las herramientas computacionales, que ofrecen enfoques complementarios cuando las técnicas clásicas resultan un desafío. En conjunto, estos esfuerzos contribuyen a construir una base de conocimiento sólida que facilite la posterior traslación de los resultados."],"dc:format":["application/pdf"],"dc:identifier":["https://dialnet.unirioja.es/servlet/oaites?codigo=399607"],"dc:language":["eng"],"dc:publisher":["Universidad de La Rioja (España)"],"dc:rights":["LICENCIA DE USO: Los documentos a texto completo incluidos en Dialnet son de acceso libre y propiedad de sus autores y/o editores. Por tanto, cualquier acto de reproducción, distribución, comunicación pública y/o transformación total o parcial requiere el consentimiento expreso y escrito de aquéllos. Cualquier enlace al texto completo de estos documentos deberá hacerse a través de la URL oficial de éstos en Dialnet. Más información: https://dialnet.unirioja.es/info/derechosOAI | INTELLECTUAL PROPERTY RIGHTS STATEMENT: Full text documents hosted by Dialnet are protected by copyright and/or related rights. This digital object is accessible without charge, but its use is subject to the licensing conditions set by its authors or editors. Unless expressly stated otherwise in the licensing conditions, you are free to linking, browsing, printing and making a copy for your own personal purposes. All other acts of reproduction and communication to the public are subject to the licensing conditions expressed by editors and authors and require consent from them. Any link to this document should be made using its official URL in Dialnet. More info: https://dialnet.unirioja.es/info/derechosOAI"],"dc:title":["Regulation of INTS-6 by post-translational modifications: exploring phosphorylation, SUMOylation and their biological relevance in Caenorhabditis elegans"],"dc:type":["text (thesis)"]},"updated_at":"2026-07-24T06:27:11Z"}