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MARGARA, Lucia

FONCyT PhD fellow
Director: Mariela Monti
E-Mail: lmargara@fcq.unc.edu.ar

PhD Thesis Topic

Analysis of MutS role in regulation of low fidelity polymerase (Pol IV) access to replication sites
Several exogenous and endogenous agents can damage DNA. If these lesions are not correctly repaired, it could lead to mutations and genomic instability. As a consequence, the organisms have developed different mechanism to prevent, repair and tolerate DNA damage. In this work, we are studying how the repair protein MutS regulates access of the error-prone DNA polymerase Pol IV to replication sites, which corresponds to a novel mechanism for maintaining replication fidelity by MutS. Particularly, we are interested in determining the molecular mechanism of this new MutS function. In this sense, our hypothesis is that MutS controls the association of Pol IV with the processivity factor β clamp, which is absolutely required for the mutagenic activity of this DNA polymerase. To study this hypothesis, we carry out biochemical, molecular-genetic and microscopic assays using as model organism the opportunistic pathogen bacteria Pseudomonas aeruginosa, both under normal growing conditions and stress situations.