Chromatin Dynamics and Cancer

Cell biology and Dynamics
Centro de Biología Molecular “Severo Ochoa” CSIC-UAM (CBMSO)

Chromatin metabolism is regulated at different levels, from the epigenetic modification of DNA and histones to the post-translational modification of proteins associated to DNA. The co-ordinated regulation of DNA Replication, Transcription and Repair is required to maintain genome stability and cell identity. Thus, the pathways controlling chromatin metabolism are commonly mutated in cancer and they constitute new promising targets for cancer treatment.

Our group is interested in elucidating how DNA Replication and Repair are regulated through the modification of proteins by ubiquitin and SUMO. We have previously described that the replisome is a SUMO-rich environment and we have proposed that this SUMOylation drives protein ubiquitination during the process of termination. Now we want to address what is the role of the collective SUMOylation of replication factors during DNA Replication. Further, we want to understand the functions of protein SUMOylation in the response to the problems arising during DNA replication, known as replication stress. Finally, we will explore the application of the SUMO pathway as a target for cancer therapy through its effects on DNA Replication and the replication stress response.

We offer a position for a student to carry out its TFM working on the mechanisms of regulation of DNA Replication by SUMO.

Selected publications:

  • Lecona E, Fernández-Capetillo O. “Targeting ATR in Cancer” Nature Reviews Cancer (2018) 18: 586-595
  • Lecona E, Fernández-Capetillo O. “An equilibrium of SUMO and Ubiquitin during DNA replication” Bioessays (2016) 38: 1209-17
  • Murga M, Lecona E, Kamileri I, Lugli N, Sotiriou S, Días M, Antón ME, Méndez J, Halazonetis T, Fernández-Capetillo O. “POLD3 is haploinsufficient for DNA replication in mice” Molecular Cell (2016) 63: 877-83.
  • Lecona E, Rodríguez-Acebes S, Specks J, López-Contreras A, Ruppen I, Murga M, Muñoz J, Méndez J, Fernández-Capetillo O. “USP7 is a SUMO deubiquitinase essential for DNA replication” Nature Structural & Molecular Biology (2016) 23: 270-7 Co-corresponding author
Biomolecules & Cell D.