- Cell and Molecular Biology
- Martine Lomax, Deputy Group Leader
- Siobhan Cunniffe
- Jennifer Anderson
- Pamela Reynolds
- Danielle Liddle
- Alanna MacGuire
- Luca Mariotti, Visiting Researcher
- Lisa Folkes, Joint with B Vojnovic
- Daniel Martins, DPhil Student
- Agata Nasilowska, DPhil Student
- Folkes Lisa K and O'Neill Peter (2013) Modification of DNA damage mechanisms by nitric oxide during ionizing radiation. Free Radic Biol Med, 58:14-25.
- Lomax M E, Folkes L K, and O'Neill P (2013) Biological Consequences of Radiation-induced DNA Damage: Relevance to Radiotherapy. Clin Oncol (R Coll Radiol).
- Wang Minli, Saha Janapriya, Hada Megumi, Anderson Jennifer A, Pluth Janice M, O'Neill Peter, and Cucinotta Francis A (2013) Novel Smad proteins localize to IR-induced double-strand breaks: interplay between TGFbeta and ATM pathways. Nucleic Acids Res, 41(2):933-42.
- Reynolds Pamela, Anderson Jennifer A, Harper Jane V, Hill Mark A, Botchway Stanley W, Parker Anthony W, and O'Neill Peter (2012) The dynamics of Ku70/80 and DNA-PKcs at DSBs induced by ionizing radiation is dependent on the complexity of damage. Nucleic Acids Res, 40(21):10821-31.
- Abdelrazzak Abdelrazek B, Stevens David L, Bauer Georg, O'Neill Peter, and Hill Mark A (2011) The role of radiation quality in the stimulation of intercellular induction of apoptosis in transformed cells at very low doses. Radiat Res, 176(3):346-55.
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Peter O'Neill's Group is looking in to the process of radiation induced cluster DNA damage. Ionising radiation may be considered as a two-edged sword since it can induce cancer and other adverse responses in normal tissue or alternatively it leads to cellular inactivation, of considerable importance in radiotherapy. The genetic material (DNA) in cells is an important target for ionising radiation s it damages the DNA. If the damage is not removed by proteins which can restore the correct genetic code, potentially harmful effects of radiation such as mutations in the genetic code may occur and lead to significant biological consequences, such as cancer or severe late effects to normal tissue. In radiation oncology it is important to kill tumour cells but minimise damage to normal tissue. An important feature of ionising radiation is its ability to cause clusters of damage sites very close to one another. These clusters are very difficult to correct for as the repair proteins do not easily recognise the damage.
The complexity of clustered damage is thought to be a major feature that determines the biological effectiveness of radiations of different quality. The research focuses on identification of the processes leading to DNA damage, the recognition and processing of DNA damage and to identify the critical lesions and repair pathways involved in the biological responses to ionizing the radiation.
The objective of the research is to understand how these clusters of damage, which are formed by ionising radiation in cells, detrimentally interfere with the maintenance of the genetic code. As a consequence the effects of human exposure to radiation may be detrimental to health or lead to tumour cell death, which is of relevance to radiation oncology.
Experimental evidence in mammalian cells for increased severity of cluster DNA damage with increasing radiation quality, as predicted by biophysical modelling. This has implicatons for the unique types of clustered damage induced by alpha particles and underpins the relevance of heir biological severity.
- the complexity of clustered DNA damage using synthetic constructs influences damage recognition by endonucleases. Evidence that cluster DNA lesions, specific to ionizing radiation, compromise the excision of damage by base excision repair enzymes. This inhibition is thought to minimise the formation of double strand breaks. The processing of clustered DNA damage in cell extracts may be stalled leading to transmissible changes to the genome.
- We have identified the complex interaction of damage excision and replication underlying the mutagenic potential of radiation type clustered damage sites, even when one lesion is non-mutagenic. A detailed description of DNA damage processing is critical for understanding the mechanisms of radiation-induced mutagenesis.
- Detailed understanding of the repair of radiation-induced DNA double strand breaks which require different proteins depending on the complexity of the damage.
- Processing of non-double strand breaks (DSB) clustered DNA damage is significantly retarded, increasing the probability that lesions may be present at replication and act as potential precursors to "de novo" DSB at replication.
- Low doses of radiation of non-transformed cells leads to stimulation of intercellular induction of apoptosis by ROS/RNS signalling in transformed cells. the findings have significant implications for the effect of environmental doses of ionizing radiation on triggering naturally occuring anticancer defence mechanisms.
- Understanding how nitric oxide may enhance sterilisation of hypoxic cells through it's ability to "fix" damage.
2007- Head of DNA Damage Group
Gray Institute for Radiation Oncology and Biology, Department of Oncology
University of Oxford
1991-2007 Group Leader of DNA Damage Group
MRC Radiation and Genome Stability Unit (formerly Radiobiology Unit)
- 2003-05 Interim Director
MRC Radiation and Genome Stability Unit
- 1983-91 Research Scientist
MRC Radiobiology Unit
Institute of Cancer Research, Sutton UK
1974-77 Post-doctoral scientist
Max-Planck-Institut für Strahlenchemie, Mülheim, Germany.
Sources of Funding
- Medical Research Council
- European Union
- US Department of Energy
Professor Peter O’Neill is MRC Senior Group Leader of the DNA Damage Group and Deputy Director of the Gray Institute of Radiation Oncology at the University of Oxford. His research has focused on the chemistry of the types of DNA damage induced by ionizing radiation, from the early free radical processes to the complexities of damage, and how these may contribute to carcinogenesis or radiation cytotoxicity. More recently his major research interests have focused on understanding the challenges that radiation-induced clustered DNA damage sites present to the repair pathways and as a consequence contribute to carcinogenesis at environmental radiation levels or to the killing of tumour cells.
Following post-doctoral positions first at the Max-Planck-Institut für Strahlenchemie in Mülheim, Germany, and then at the Institute of Cancer Research in Sutton, UK, Professor O’Neill spent 23 years carrying out research at the MRC Radiation and Genome Stability Unit (formerly Radiobiology Unit) in Harwell, Oxfordshire. He came to Oxford to lead the DNA Damage Group in 2005 and is also Course Director of the MSc course in Radiation Biology at the University of Oxford.
Professor O’Neill is Associate Editor of the International Journal of Radiation Biology and of Radiation Research and has a total of 226 peer-reviewed publications. He provides consultancy and advice to several international organisations including the European Space Agency, was recently President of the Radiation Research Society of USA, a member of the Lasers for Science (LSF) Facility Access Panel for the UK’s Science and Technology Facilities Council and serves on several international committees relating to radiation.
Awards Training and Qualifications
- 2010 Weiss Medal awarded by the ARR
- 1996 DSc, University of Leeds
- 1995 Fellow, Royal Society of Chemistry
- 1970- 1974 PhD, University of Leeds
- 1967- 1970 BSc, University of Leeds