Dr Eva Petermann PhD

Dr Eva Petermann

Institute of Cancer and Genomic Sciences
Senior Lecturer

Contact details

Address
Institute of Cancer and Genomic Sciences
Institute for Biomedical Research (West)
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Dr Petermann’s research focuses on mechanisms of mammalian replication stress and the interactions between DNA replication and the DNA damage response. She has published more than 25 research papers and review articles in this area. Her lab has received research funding from the MRC, Worldwide Cancer Research, Cancer Research UK, the Royal Society and the Wellcome Trust.

Research group page: https://www.evapetermann.org/

Research group members:

Dr Ann Liza Piberger (A.L.Piberger@bham.ac.uk)
Mr Kacper Wozniak
Mr Akhil Bowry 

The Petermann group is a member of the Birmingham Centre for Genome Biology.

Qualifications

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

Biography

Eva Petermann qualified in 2001 with a BSc and MSc in Biochemistry at the Martin Luther University Halle-Wittenberg in Germany. She obtained her PhD in 2004 at the Free University of Berlin, where she worked on the biochemistry of DNA base excision repair.

She 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. In her next postdoctoral position she worked with Thomas Helleday at the Gray Institute for Radiation Oncology and Biology at the University of Oxford, where she also was a Junior Research Fellow at Linacre College.

Dr Petermann joined the University of Birmingham as a Lecturer in 2010. She received the European Environmental Mutagen Society Young Scientist Prize in 2010. 

Teaching

Postgraduate supervision

Dr Petermann is interested in supervising doctoral research students in the following areas:

  • Deregulation of DNA replication and genomic instability 
  • The DNA damage response to replication inhibitors

If you are interested in studying any of these subject areas please contact Dr Petermann on the contact details above, or for any general doctoral research enquiries, please email: dr@contacts.bham.ac.uk or call +44 (0)121 414 5005.

For a full list of available Doctoral Research opportunities, please visit our Doctoral Research programme listings.

Research

Research Themes

DNA Replication, DNA Damage and Repair, Cancer Genetics and DNA damage, Genome Biology

Research Activity

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)

 

Publications

Bowry A, Piberger AL, Rojas P, Saponaro M, Petermann E (2018) BET inhibition induces HEXIM1- and RAD51-dependent conflicts between transcription and replication. Cell Reports 25: 2061–2069 

Benedict B, van Harn T, Dekker M, Hermsen S, Kucukosmanoglu A, Pieters W, Delzenne-Goette E, Dorsman JC, Petermann E, Foijer F, & Te Riele H (2018) Loss of p53 suppresses replication-stress-induced DNA breakage in G1/S checkpoint deficient cells. Elife 7:e37868. 

Bayley R, Blakemore D, Cancian L, Dumon S, Volpe G, Ward C, Almaghrabi R, Gujar J, Reeve R, Raghavan M, Higgs M, Stewart GS, Petermann E, Garcia P(2018)MYBL2 supports DNA double strand break repair in haematopoietic stem cells. Cancer Res 78: 5767-5779. 

Ronson GE, Piberger AL, Higgs MR, Olsen AL, Stewart GS, McHugh PJ, Petermann E, Lakin ND (2018) PARP1 and PARP2 stabilise replication forks at base excision repair intermediates through Fbh1-dependent Rad51 regulation. Nature Communications 9: 746

Kotsantis P, Petermann E, & Boulton SJ (2018) Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place. Cancer Discovery 8: 537-555. 

Kotsantis P, Marques Silva L, Irmscher S, Jones RM, Folkes L, Gromak N, Petermann E (2016) Increased global transcription activity as a mechanism of replication stress in cancer. Nature Communications 7: 13087 

Kotsantis P, Jones RM, Higgs MR, Petermann E (2015) Cancer therapy and replication stress: forks on the road to perdition. Adv Clin Chem 69: 91-138 

Jones RM, Kotsantis P, Stewart GS, Groth P, Petermann E (2014) BRCA2 and RAD51 promote double-strand break formation and cell death in response to Gemcitabine. Mol Cancer Ther 13: 2412-2421  

Jones RM, Mortusewicz O, Afzal I, Lorvellec M, Garcia P, Helleday T, Petermann E (2013) Increased replication initiation and conflicts with transcription underlie Cyclin E-induced replication stress. Oncogene 32:3744-3753 

Petermann E, Helleday T (2010) Pathways of mammalian replication fork restart. Nat Rev Mol Cell Biol 11: 683-687

Petermann E, Orta ML, Issaeva N, Schultz N, Helleday T (2010) Hydroxyurea-stalled replication forks become progressively inactivated and require two different RAD51- mediated pathways for restart and repair. Mol Cell 37: 492-502