(...) The goal of this project is to study how the S phase checkpoint protects replication against genotoxic reagents or conditions. This work will be carried out in the budding yeast \i Saccharomyces cerevisiae\i0 , the eukariotic organism in which chromosomal replication is best defined at he molecular level. We propose two objectives. We will first study the block of origin firing throug the inhibition of Dbf4-Cdc7. The activation of the S phase checkpoint results in the Rad53-dependent hyperphosphorylation of Dbf4. We will generate non-phosphorylable mutants and study whether origin block control is lost. We will also study whether such loss of block control results in genomic instability. Secondly, we propose to identify new targets of the S phase checkpoint. In a first phase we will undertake an open strategy, involving biochemical and genetic methods. We will then study in depth the role of checkpoint control on the identified targets.
|Effective start/end date||1/10/06 → 30/09/07|