José A. Tercero
Maintenance of genome integrity during chromosome replication and fidelity of DNA synthesis are essential for the correct transmission of genetic information to daughter cells. Inevitably, the complexity of chromosome replication is exacerbated by DNA damage, which constitutes a source of errors and a challenge for the normal progression and the stability of replication forks. Successful genome duplication in every cell cycle requires protection of replication forks, repair or tolerance of DNA lesions, and the ability to resume DNA synthesis after fork blocks. Failures in these processes lead to genomic instability and reduce cell survival.

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 DNA repair and damage tolerance proteins, in conjunction with different helicases and nucleases, facilitate chromosome replication in the presence of DNA lesions or replication perturbations. We analyse the contribution of all these proteins to the integrity and function of replication forks. We study their regulation and relative importance for cell viability under different conditions and types of DNA insults, as well as the connections among them and with replication and checkpoint proteins. Our working model is the budding yeast Saccharomyces cerevisiae, although the main aspects of these processes are evolutionarily conserved.

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Figure 1: Some DNA repair proteins accumulate and form foci after treatment of budding yeast cells in S phase with DNA damaging agents