Endogenous metabolic products, such as reactive oxygen species, and exogenous physical and chemical genotoxic stress, constantly assault the genetic material of our cells. It is estimated that there are 100.000 lesions per cell per day in a human body. In response to such a high levels of DNA damage, sophisticated mechanisms have evolved to coordinate cell cycle progression with DNA repair. When those systems fail or the rate of DNA damage exceeds the capacity of the cell to repair it, the accumulation of errors can overwhelm the cell and result in early senescence, apoptosis, or cancer.

In our group, we are focussed on the cellular response that takes place after the formation of a DNA lesion. In response to a DNA break, a damage signal is triggered to activate the processing of the broken DNA ends, the searching for an intact homologous DNA sequence and the copying of the lost genetic information. While the importance of protein phosphorylation along these steps has been well documented over the last years, the complex role of protein dephosphorylation remains to be investigated. Thus, we are interesting to decipher the distinctive role of protein phosphatases in the DNA repair pathway, their regulation during the damage response and their targets in the process.

To answer these questions, we use biochemical, microscopy and genetic approaches to follow the timely execution of every individual step of the repair process. The combination of these classical techniques with a new set of genome-wide methodologies, allow us to gather information about the importance of protein dephosphorylation in the maintenance of genome integrity in response to a DNA lesion.

Analysis of DNA repair
A) Cells repair a DNA lesion by activation of a set of processes that end up with the efficient reconstitution of the DNA molecule.
B) The dynamics in the repair of a DNA lesion can be followed by using genome-wide sequencing approaches.
C) The computational analysis of the data obtained from the genomic sequences allow us to modelling the evolution of the DNA lesion along the damage response.
D) Genome-wide recombination events between different chromosomes can efficiently be measured after the formation of a single DNA break.
E) The analysis of the frequency in chromosome recombination can be used to infer the ability of chromosomes to interact with each other in response to a DNA lesion.