CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Development of Screening Methods to Identify Translesion DNA Synthesis Inhibitors.
Autor/es:
GARCIA I.A.; BOCCO J.L.; PANSA M.F.; SORIA G.; VILLAFAÑEZ M.F.; CARBAJOSA S.
Lugar:
Córdoba
Reunión:
Congreso; 52° Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular - SAIB 2016.; 2016
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular
Resumen:
Translesion DNA synthesis (TLS) is a DNA damage tolerance process that employs specialized polymerases to bypass DNA damage during replication. Recent evidence indicates that TLS is a key process that promotes the development of resistance to cancer treatments that induce DNA damage. Thus, the inhibition of TLS emerges as a promising strategy for cancer therapy. However, specific chemical inhibitors of TLS are not available. The main goal of our project is to identify specific inhibitors of TLS that can be used as ―a proof of concept‖ in cancer therapy. Our rational is that since TLS polymerases recruitment to sites of DNA damage is a key step for TLS success, we can indirectly monitor TLS efficiency by studying two key markers: 1) The mono-ubiquitylation of PCNA and 2) the accumulation of a TLS polymerase into replication foci. We thus developed two screening methods that allow us to promptly identify inhibitors of these markers through a Western-Blot based platform to follow the mono-ubiquitylation of PCNA and imaging-based assay for the quantification of TLS polymerase foci. In this poster we describe the results of a pilot screening using an open source library of kinase inhibitors from Glaxo Smith Kline and the early validation of the identified hits.