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Coordination between RNAPII transcription and DNA replication


   Institute of Cancer and Genomic Sciences

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  Dr M Saponaro  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 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.


Funding Notes

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

References

Wang et al., Persistence of RNA transcription during DNA replication delays duplication of transcription start sites until G2/M. Cell Reports 2021 Feb 16;34(7):108759.
M Saponaro et al., RECQL5 controls transcript elongation and suppresses genome instability associated with transcription stress. Cell 2014 May 22;157(5):1037-49.
L Williamson, et al., UV irradiation induces a non-coding RNA that functionally opposes the protein encoded by the same gene. Cell 2017 Feb 23;168(5):843-855.e13.
T Kantidakis et al., Mutation of cancer driver MLL2 results in transcription stress and genome instability. Genes & Development 2016 Feb 15;30(4):408-20.

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