- Cell and Molecular Biology
- Martine Lomax, Deputy Group Leader
- Siobhan Cunniffe
- Jennifer Anderson
- Pamela Reynolds
- Timea Palmai-Pallag
- Danielle Liddle
- Luca Mariotti, Visiting Researcher
- Lisa Folkes, Joint with B Vojnovic
- Sarah Cooper, DPhil student
- Daniel Martins, DPhil Student
- Agata Nasilowska, DPhil Student
- Abdelrazzak Abdelrazek B, O'Neill Peter, and Hill Mark A (2011) Intercellular induction of apoptosis signalling pathways. Radiat Prot Dosimetry, 143(2-4):289-93.
- 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.
- Eccles Laura J, O'Neill Peter, and Lomax Martine E (2011) Delayed repair of radiation induced clustered DNA damage: friend or foe? Mutat Res, 711(1-2):134-41.
- Anderson JA, Harper JV, Cucinotta FA, and O'Neill P (2010) Participation of DNA-PKcs in DSB repair following exposure to high and low LET radiation Radiat. Res, 174:195-205.
- Botchway SW, Reynolds P, Parker AW, and O'Neill P (2010) Use of near infrared femtosecond lasers as sub-micron radiation microbeam for cell damage and repair studies Mutat Res, 704 (1-3):38-44.
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Peter O’Neill’s Group is looking into the processing of radiation-induced clustered 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 as 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 radiation.
The objective of the research is to understand how these clusters of damage, which are formed by ionising radiation in cells, detrimentally interfer with maintenance 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 clustered DNA damage with increasing radiation quality, as predicted by biophysical modelling. This has implications for the unique types of clustered damage induced by alpha particles and underpins the relevance of their 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.
Base lesions close to the end of DNA double strand breaks greatly reduces the efficiency of break rejoining by non-homologous recombination.
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 a triggering naturally occurring anticancer defence mechanisms
2007- Head of DNA Damage Group
Department of Radiation Oncology Biology
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
Awards Training and Qualifications
- 1996 DSc, University of Leeds
- 1995 Fellow, Royal Society of Chemistry
- 1970- 1974 PhD, University of Leeds
- 1967- 1970 BSc, University of Leeds