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Transcription replication coordination

Institute of Cancer and Genomic Sciences

Applications accepted all year round Self-Funded PhD Students Only

About the Project

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 them 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.

Funding Notes

Self-funded and self-funded/government-funded UK and international PhD students


RECQL5 controls transcript elongation and suppresses genome instability associated with transcription stress. M Saponaro et al., Cell 157 (5), 1037-1049, 2014

UV irradiation induces a non-coding RNA that functionally opposes the protein encoded by the same gene L Williamson, M Saponaro, et al., Cell 168 (5), 843-855. e13, 2017

Mutation of cancer driver MLL2 results in transcription stress and genome instability. T Kantidakis, M Saponaro et al., Genes & development 30 (4), 408-420, 2016

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