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Investigating the role of RNaseH2B in the response to oncogene-induced replication stress


Project Description

Applications are invited for a 4-year fully-funded PhD Studentship starting October 2020.

Replication stress is an important source of genomic instability in cancer. Oncogenes can induce replication stress, which then activates a DNA damage response that can be a potential target for cancer therapy. We are interested in how hyper-stimulation of transcription by oncogenes such as RAS can lead to conflicts between transcription and replication, and how cancer cells overcome these conflicts. We are offering a CR-UK funded research project to investigate new DNA damage responses to transcription-replication conflicts, and how this is de-regulated in cancers. These mechanisms may be critical in cancer development and for the development of better cancer therapies.

Person Specification
Applicants should have a strong, demonstrable, background in molecular biology or biochemistry. They should be able to demonstrate prior competence in a laboratory environment and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in Biology or Biochemistry, or in Biomedical subjects having options in biochemistry or molecular biology.
How to apply
Informal questions should be directed to Dr Eva Petermann: . Applications should be directed to David Piela: .
To apply, please send:
• A Detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree transcripts;
• Evidence of your proficiency in the English language, if applicable.

Applicants will be required to attend an interview in March. This will include meeting the research group and a tour of the labs. While the interview can be conducted by telephone or skype, face –to –face is ideal.

Funding Notes

This PhD is funded by Cancer Research UK and includes bench fees, tuition fees and a living stipend ~£19,000 pa.

References

Jones, R.M., Mortusewicz, O., Afzal, I., Lorvellec, M., Garcia, P., Helleday, T. & Petermann, E. Increased replication initiation and conflicts with transcription underlie Cyclin E-induced replication stress. Oncogene 32, 3744-3753 (2013).
Kotsantis, P., Silva, L.M., Irmscher, S., Jones, R.M., Folkes, L., Gromak, N. & Petermann, E. Increased global transcription activity as a mechanism of replication stress in cancer. Nature communications 7, 13087 (2016).
Bowry, A., Piberger, A.L., Rojas, P., Saponaro, M. & Petermann, E. BET Inhibition Induces HEXIM1- and RAD51-Dependent Conflicts between Transcription and Replication. Cell reports 25, 2061-2069 e2064 (2018).

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