Maintenance of genome integrity during chromosome replication

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

Our group studies the mechanisms by which eukaryotic cells prevent genomic instability, an important cause of ageing, developmental abnormalities and diseases such as cancer. We mainly study how genome integrity is maintained during chromosome replication, especially under conditions of DNA damage or replicative stress. The basic aspects of these processes are evolutionarily conserved, which allows us to use the budding yeast Saccharomyces cerevisiae as a model organism. Currently, we focus our research on the study of the regulation and function of mechanisms of DNA damage tolerance and endonucleases involved in the DNA damage response. For this, we use a combination of molecular biology, cell biology, biochemical and genetic approaches.


DNA damage tolerance

Figure 1. Schematic illustration of the processes triggering the DNA damage tolerance response at replication forks (see Saugar et al., 2014).  




  nuclease pict
  Fig. 2. The activity of the Mus81-Mms4 endonuclease is strictly regulated during the cell cycle by CDK- and PLK-dependent phosphorylation of the non-catalytic subunit Mms4. 

Recent publications

- Saugar I, Jiménez-Martín A, Tercero JA (2017) "Subnuclear relocalization of structure-specific endonucleases in response to DNA damage". Cell Rep. 20: 1553-1562.

- 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.

- Ortiz-Bazán MA, Gallo-Fernández M, Saugar I, Jiménez-Martín A, Vázquez MV, Tercero JA (2014) “Rad5 plays a major role in the cellular 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.

- 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.

- Gallo-Fernández M, Saugar I, Ortiz-Bazán MA, Vázquez MV, Tercero JA (2012) “Cell cycle-dependent regulation of the nuclease activity of Mus81-Eme1/Mms4”.  Nucleic Acids Res. 40: 8325-8335.

Biomolecules & Cell D.
Molecular Biomedicine
José Antonio Tercero