DNA replication control by post-translational modifications: ubiquitination and phosphorylation

Abstract

In order to maintain genomic integrity and avoid mutation, cells have developed efficient mechanisms to control the cell cycle and repair damage, besides controlling extensively the process involves in genome duplication (S phase of the cell cycle) and the division of the two daughter cells (mitosis). Deficiency in all of these mechanisms can produce genomic instability and is associated with pathological diseases. For example, mutations in genes implicated in preserving genome stability are the root cause of the uncontrolled division in tumour cells. Therefore, the study of the process that controls genomic integrity is the key to understand the cause of cancer. In spite of all the knowledge about these processes acquired throughout the last years, there are still many questions yet to answer, in particular about the role of post-translational mofications in controlling the proteins involved in these mechanisms. Thus, supported by our recent publication and preliminary results we propose to identify new regulators of the DNA replication. More specifically, we will focus on identifying potential ubiquitin hydrolases (DUBs) acting on different pre-replicative proteins, involved in the origins licensing of replication and the study od the unfolding protein response "UPR". Once studied the UPR and identified the DUBs, we will try to understand their regulatory mechanisms and their implications in the development of tumours.