GENERAL INTEREST

The former name of this Unit was "Cellular proliferation and differentiation".

Four former sublines of the Unit have moved in the last years to the Institute of Molecular and Cellular Biology of Cancer (IBMCC), Salamanca. Another subline has discontinued its activity. Furthermore, one more group (line 3) has already applied to move to IBMCC.

In addition, four emerging groups have recently joint Unit II.

The general aim of Line 2 is to better understand some of the key players and the molecular mechanisms that regulate the interplay between DNA replication, DNA repair and recombination, as well as their potential relationship with other genomic activities, such as transcription and epigenetic modifications of chromatin. In particular, we will investigate the genetic and epigenetic determinants of ORI specification and function and how cells respond to accidental or programmed DNA damage and how this response is influenced by chromatin organization. The mechanisms governing initiation of meiotic recombination and the genomic distribution of meiotic recombination events will be also examined. To carry out these studies genetic, biochemical, microscopic, bioinformatic and genomic approaches will be used in several model systems ranging from budding and fission yeasts to mouse and human cells.

Another goal of Line 2 is to understand the mechanisms of replication and expression of RNA narnaviruses of Saccharomyces cerevisiae. Reverse genetic analysis applied to the study of these viruses will give information about the cis and trans-acting signals that allow them to infect the host persistently, but also the work can be approached from the point of view of the host, isolating or identifying factors involved in their maintenance or control.. Of a particular interest is the role played in this control by the host nucleases involved in the cellular mRNAs turnover. The simplicity of the narnavirus genomic organization (with only one protein encoded in their genomes), the possibility to do reverse genetics as well as the fact that they infect S. cerevisiae where molecular, biochemical, and genetic studies can be undertaken easily makes them a good model system where to study how RNA-dependent RNA polymerases (enzymes of exclusively viral origin) work.

Another subline of Line 2 is to investigates some of the mechanisms that regulate transcription and how the connections between transcription by RNAPII and other nuclear processes might regulate gene expression in general. Therefore, the studies are focused on the following aspects of mRNA biogenesis: RNAPII-CTD phosphorylation regulation by the transcriptional activator Sub1, transcription elongation and connections between transcription and other nuclear processes.