Transcription regulation in the context of genome stability

The DNA in our cells is a substrate for both RNA Pol II (RNAPII) transcription and DNA replication. Consequently, only one of the two processes can use the DNA as a template at any given time. There are indeed instances during the cell cycle, in the S-phase, when these two processes coexist. We know that the two processes of RNAPII transcription and DNA replication are somehow connected together and need we know that the RNAPII transcription can induce genome instability, and genome instability is greatly increased in contexts with a defective transcription. It has also been shown how in these contexts DNA replication is impaired leading to genome instability.

The relevance of this problem is huge, not only because a fundamental question at the heart of the cell biology, but also because these processes can directly impact on human health, being associated with cancer development and neurological disorders. Over the years, a lot of attention has been addressed in identifying transcription-associated factors that present increased genome instability. However the global impact of normal RNAPII transcription on DNA replication has been largely ignored. We intend answering how transcription and replication manage to coexist on the DNA without interfering with each other. We are also interested in characterising how these processes can crosstalk to influence each other. In order to deliver these complex answers, we make use of a combination of multi-disciplinary, cutting edge approaches combining genome-wide next generation sequencing approaches and functional study, in human immortalised cell lines.