Dr Eva Petermann PhD

• PG Cert Learning and Teaching in Higher Education, 2012
• PhD in Biochemistry, 2004 
• BSc/MSc in Biochemistry, 2001

Career to date

2020 -          Reader in Genome Biology, University of Birmingham

2014 - 2020 Senior Lecturer, University of Birmingham

2010 - 2014 Lecturer, University of Birmingham

2007 - 2010 Postdoctoral researcher, University of Oxford

2004 - 2007 Postdoctoral researcher, University of Sussex

External Engagement

2021 -           Editorial Board, British Journal of Cancer

2020 - 2022 Conference Theme Panel RAI, Biochemical Society

2013 -            UK Genome Stability Network Committee

Member of funding committee

Member of junior PI recruitment panel

• Medicine and Surgery MBChB - BMS Year 1 "Research taster"
• Medicine and Surgery MBChB - BMS Year 2 "Cancer - causes to cures"
• BMedSc – Year 2 "Advanced molecular and experimental genetics
• BMedSc – Year 3 “New targets and drugs in cancer therapy”
• BMedSc – Year 3 “DNA damage pathways in human disease”
• BSc (Biosciences) – Year 3 “Cancer biology”
• MSc Clinical Oncology “Radiation biology”

Dr Petermann is interested in supervising doctoral researchers in
the following areas:

- Fundamental mechanisms of DNA replication stress and DNA repair
- Oncogene-induced replication stress
- Conflicts between replication and transcription
- Targeted cancer therapies
- Cancer chemotherapy and replication stress

General doctoral research enquiries: mds-gradschool@contacts.bham.ac.uk

DNA replication is the process by which dividing cells copy their genetic information. Replication is very important but also dangerous for cells, because if obstacles inhibit the movement of the replication apparatus, this can lead to DNA damage, mutations or cell death. This is called replication stress (Jones and Petermann, 2012). My group investigates molecular mechanisms of replication stress in cancer development and -treatment.

Transcription-replication conflicts in cancer

Replication stress, or replication-associated DNA damage, occurs frequently in cancer. There is a growing interest in targeting oncogene-induced replication stress for cancer therapy. Effective targeting will require mechanistic understanding of how oncogenes induce replication stress. It is widely appreciated that oncogenes can promote replication stress by de-regulating the cell cycle machinery to increase proliferation. However to promote proliferation, oncogenes also need to hyper-activate the basal transcription machinery. We use DNA fibre approaches to identify new mechanisms of oncogene-induced replication stress (Jones et al., 2013, Kotsantis et al., 2016, Bowry et al., 2021).

We have evidence for transcription hyper-activation as an alternative and important replication stress mechanism. We recently reported that H-Ras^V12 induces replication-transcription conflicts, not by de-regulating the cell cycle, but by increasing expression of a general transcription factor (TBP) and global RNA synthesis (Kotsantis et al., 2016, Bowry et al., 2021). We showed that TBP overexpression can promote replication stress independently of oncogenes.  We are further investigating the mechanisms of oncogene-induced transcription-replication conflicts. We are also investigating transcription-replication conflicts induced by a new class of cancer drugs called BET inhibitors (Da Costa et al., 2013; Bowry et al., 2018).

Homologous recombination at stalled replication forks

Homologous recombination (HR) is a remarkable genome maintenance pathway that brings together DNA replication and DNA repair. Because of this, it is absolutely central to diseases characterized by replication stress or treated with replication stress-inducing agents. 

It is increasingly evident that HR processes frequently occur at perturbed replication forks, where HR performs novel roles that are distinct from its classic function in DNA double-strand break repair. New insights into the roles of HR at stressed replication forks are relevant for cancer development and therapy. We are particularly interested in understanding how HR can slow and stall forks.

We use DNA fibre approaches to identify new roles for HR and the central HR factor RAD51 at stalled replication forks. We study how RAD51 modulates fork progression in response to classic chemotherapy, targeted cancer therapies, and environmental mutagens (Jones et al, 2014; Ronson et al., 2018; Piberger et al., 2020)