Colleges, School and Institutes
I qualified in 2001 with a BSc and MSc in Biochemistry at the Martin Luther University Halle-Wittenberg in Germany and then obtained a PhD in Biochemistry (2004) at the Free University Berlin, where I worked on PARP1 and DNA base excision repair.
I continued with postdoctoral research in the field of DNA repair and replication in the lab of Keith Caldecott at the Sussex Centre for Genome Damage and Stability in Brighton and then moved to the lab of Thomas Helleday at the University of Oxford, where I was also a Junior Research Fellow at Linacre College.
I joined the University of Birmingham as a Lecturer in 2010. I received the European Environmental Mutagen Society Young Scientist Prize in 2010. In 2019, the Petermann lab was awarded £1.6 million in funding from Cancer Research UK and the Medical Research Council.
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; Petermann and Helleday, 2010). 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).
We have evidence for transcription hyper-activation as an alternative and important replication stress mechanism. We recently reported that H-RasV12 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). 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 (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)
Willingness to take PhD students
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