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Defining the transcription roles of BRCA1 and BRCA2


   Institute of Cancer and Genomic Sciences

   Applications accepted all year round  Self-Funded PhD Students Only

About the Project

BRCA1 and BRCA2 mutations predispose to both breast and ovarian cancers, with both factors playing many crucial roles in DNA damage repair and response. BRCA1 and BRCA2 are essential to maintain genome stability, however, both factors are also involved in regulating the RNA Pol II transcription process. What is the contribution of the transcription roles of BRCA1 and BRCA2 to genome stability maintenance and the impact on disease, is, unfortunately, less characterised and understood.

Using a combination of molecular biology, biochemistry, functional genomics, and bioinformatics, the student will assess how exactly BRCA1 and BRCA2 regulate RNA Pol II transcription, how this role affects the production of transcripts, and how these roles are important to preserve genome stability and are important to sensitise cells to specific drugs.


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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