RNA Pol II (RNAPII) transcription and DNA replication are the two essential-for-life processes that use as a substrate the DNA in our cells, allowing the¬¬m to express the content of their genetic information and to propagate these instructions to daughter cells. However, DNA can be engaged by only one of these processes at any given time and we know that transcription can impair DNA replication inducing increased DNA damage and genome instability. In contexts of defective transcription this instability is furthermore greatly increased. Importantly, transcription-induced genome instability has also a direct impact on human health as it is associated with cancer development and neurological disorders.
Using a combination of molecular biology, biochemistry, functional genomics and bioinformatics, the student will assess how these two processes can co-exist in the genome and how exactly in disease-related contexts transcription can become an impairment for DNA replication, inducing DNA damage and genome instability.