Regulación de la replicación del ADN por la modificación colectiva del replisoma

Pardo Melero, Antonio (2019). Regulación de la replicación del ADN por la modificación colectiva del replisoma. Proyecto Fin de Carrera / Trabajo Fin de Grado, E.T.S. de Ingeniería Agronómica, Alimentaria y de Biosistemas (UPM), Madrid.

Description

Title: Regulación de la replicación del ADN por la modificación colectiva del replisoma
Author/s:
  • Pardo Melero, Antonio
Contributor/s:
  • Lecona Sagrado, Emilio
  • Oñate Sanchez, Luis
Item Type: Final Project
Degree: Grado en Biotecnología
Date: July 2019
Subjects:
Faculty: E.T.S. de Ingeniería Agronómica, Alimentaria y de Biosistemas (UPM)
Department: Biotecnología - Biología Vegetal
Creative Commons Licenses: Recognition - No derivative works - Non commercial

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Abstract

DNA replication mediates the copy of the genetic information in a cell for its transmission to daughter cells. This process is particularly vulnerable and problems during DNA replication can promote genomic instability. Our knowledge of the mechanisms that ensure the faithful duplication of the DNA during the process of replication have vastly increased in the last years, highlighting the role of post- translational modifications (PTMs) such as modification by Ubiquitin and SUMO (Small Ubiquitin-like modifier) in this process. The proteomic characterization of the nascent chromatin has recently revealed the existence of a SUMO-rich and Ub-poor environment at replication forks while mature chromatin shows the opposite pattern, although the biological relevance of this environment remains to be explored. Interestingly, it has been recently proposed that the modification of proteins in the same complex or pathway by SUMO may be necessary to elicit a robust biological response, in what has been called the group modification model for the action of SUMO. Here we show that the depletion of SUMOylated proteins hinders DNA replication, supporting a role for the group modification of the replication machinery at replication forks. The defect in DNA replication leads to a delay in the progression through S phase without the induction of replication stress or DNA damage. We have not detected major changes in the localization of replication factors to chromatin in the absence of SUMO conjugation. Using iPOND, we have confirmed that the replisome is effectively depleted of SUMOylated proteins under these conditions and further experiments will be required to determine if the depletion of SUMOylated proteins affects the composition of the replisome. In addition, we set up the conditions to immunoprecipitate SUMOylated proteins from chromatin fractions and our preliminary results indicate that TIMELESS or MCM3 could be SUMOylated. Finally, we have shown that the depletion of SUMO conjugation does not affect the replication stress response and we did not detect any changes in the activation of ATR and the signaling in this pathway induced by different stress agents. In the future we will dissect the mechanisms through which SUMO regulates the dynamics of DNA replication, trying to determine if the SUMO pathway is a potential target in tumors that present defects in the pathway of homologous recombination.

More information

Item ID: 57078
DC Identifier: http://oa.upm.es/57078/
OAI Identifier: oai:oa.upm.es:57078
Deposited by: Biblioteca ETSI Agrónomos
Deposited on: 25 Oct 2019 12:18
Last Modified: 25 Oct 2019 12:18
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