Saturday, 23rd June 2018

Genome Dynamics and Function

      Chromosome replication and genome stability




José Antonio Tercero



Research summary:

The maintenance of genome integrity during chromosome replication and the fidelity of DNA synthesis are essential for the correct transmission of genetic information in every cell division cycle. Inevitably, chromosome replication is threatened by DNA damage, which is a potential source of errors and a risk for the stability and progression of replication forks. Successful genome duplication in every cell cycle requires the repair or tolerance of DNA lesions, the protection of replication forks, and the ability to resume DNA synthesis after fork stalling. Failures in these processes lead to genomic instability, a hallmark of cancer and other diseases, as well as an important causal factor in aging.

Our group is interested in understanding how eukaryotic cells maintain genome stability during chromosome replication, especially under conditions that cause DNA damage or replicative stress. We study how different DNA repair, DNA damage tolerance and checkpoint proteins, in conjunction with some helicases and nucleases, facilitate chromosome replication in the presence of DNA lesions or replication perturbations. We analyse the contribution of these proteins to the integrity and function of replication forks, their regulation and their importance for cell viability under different conditions that cause DNA damage. The main aspects of these processes are evolutionarily conserved, allowing us to use the budding yeast Saccharomyces cerevisiae as a working model organism. 


Recent Publications:

  • Gallo-Fernández M, Saugar I, Ortiz MA, Vázquez MV, Tercero, JA (2012) “Cell cycle-dependent regulation of the nuclease activity of Mus81-Eme1/Mms4”. Nucleic Acids Res. 40: 8325-8335.
  • Saugar I, Vázquez MV, Gallo-Fernández M, Ortiz-Bazán MA, Segurado M, Calzada A, Tercero JA (2013) “Temporal regulation of the Mus81-Mms4 endonuclease ensures cell survival under conditions of DNA damage”. Nucleic Acids Res. 41: 8943-8958.
  • Ortiz-Bazán MA, Gallo-Fernández M, Saugar I, Jiménez-Martín A, Vázquez MV, Tercero JA (2014) “Rad5 plays a major role in the celular response to DNA damage during chromosome replication”. Cell Rep. 9: 460-468.
  • Saugar I, Ortiz-Bazán MA, Tercero JA (2014) “Tolerating DNA damage during eukaryotic chromosome replication” Exp. Cell Res. 329: 170-177.
  • Morafraile EC, Diffley JFX, Tercero JA*, Segurado M* (2015) “Checkpoint-dependent RNR induction promotes fork restart after replicative stress”. Sci. Rep 5: 7886. *Corresponding authors
  • Saugar I, Jiménez-Martín A, Tercero JA (2017) "Subnuclear relocalization of structure-specific endonucleases in response to DNA damage. Cell Rep20: 1553-1562.


* If you are interested in joining our group, please write to: This email address is being protected from spambots. You need JavaScript enabled to view it.