Regulation of INTS-6 by post-translational modifications: exploring phosphorylation, SUMOylation and their biological relevance in Caenorhabditis elegans

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.

Grantor dc:publisher

Universidad de La Rioja (España)

Year dc:date

2026

Author dc:creator

• Romero Aranda, Cristina

Contributors dc:contributor

• Cabello Pardos, Juan (null)
• Gómez Orte, Eva (null)

Statement dc:rights

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Language dc:language

eng

Repository record dc:identifier

https://dialnet.unirioja.es/servlet/oaites?codigo=399607

OAI identifier oai:identifier

oai:dialnet.unirioja.es:TES0000023232