Page 6 - 2014 Printable Abstract Book
P. 6
Failla Lecture
(AL01) DNA damage/repair, like love, depends on the right chemistry
Peter O'Neill CR-UK/MRC Oxford Institute for Radiation Oncology, Oxford, United Kingdom
During this talk, I will take us on a journey through the development of some of the important concepts
in which the chemistry of radiation-induced DNA damage has and still is making major impacts, using
examples, often undertaken in collaboration with biophysicists and biologists. The journey starts from the
early concept that the various biological effects of ionizing radiation are thought to be a consequence of
the chemical modifications in DNA initiated by free radical interactions. However, over the past couple of
decades these concepts have been refined showing that the patterns of the discrete energy depositions
during passage of a track of ionizing radiation define the spatial distribution of lesions induced in DNA,
with a fraction of the DNA damage sites containing clusters of lesions, formed over a few nanometers.
The heterogeneous distribution of DNA lesions, some of which are in clusters, have opened up exciting
avenues. For instance biophysical approaches coupled with radiation-chemical understanding of DNA
damage have led to the concept that clusters of DNA lesions represent a signature of ionizing radiation.
More recently, a central theme of our research has been to provide experimental evidence that such
clusters of DNA lesions are indeed formed in mammalian cells and as a consequence they compromise
the ability of the cellular repair machinery to recognize and process them. Evidence indicates that delayed
repair of clustered DNA damage may lead to the formation of mutations, chromosomal aberrations and
genetic instability. The research area is still in its infancy, although emerging evidence indicates that
clustered damage sites may contribute, in part, to understanding the basis of low dose health effects of
radiation. As we approach the end of our journey I will focus on the spatiotemporal dynamics of the DNA
damage/repair processes which complements the extensive biochemical knowledge on the repair of
radiation-induced lesions including DNA double strand breaks. To date, biological thinking has tended to
predominate in understanding DNA damage repair pathways however knowledge of recruitment of
proteins in real time to DNA damage have opened up novel thinking . I hope I will have stimulated your
thinking by showing some examples on how DNA damage/repair does depend on the right chemistry.
4 | P a g e
(AL01) DNA damage/repair, like love, depends on the right chemistry
Peter O'Neill CR-UK/MRC Oxford Institute for Radiation Oncology, Oxford, United Kingdom
During this talk, I will take us on a journey through the development of some of the important concepts
in which the chemistry of radiation-induced DNA damage has and still is making major impacts, using
examples, often undertaken in collaboration with biophysicists and biologists. The journey starts from the
early concept that the various biological effects of ionizing radiation are thought to be a consequence of
the chemical modifications in DNA initiated by free radical interactions. However, over the past couple of
decades these concepts have been refined showing that the patterns of the discrete energy depositions
during passage of a track of ionizing radiation define the spatial distribution of lesions induced in DNA,
with a fraction of the DNA damage sites containing clusters of lesions, formed over a few nanometers.
The heterogeneous distribution of DNA lesions, some of which are in clusters, have opened up exciting
avenues. For instance biophysical approaches coupled with radiation-chemical understanding of DNA
damage have led to the concept that clusters of DNA lesions represent a signature of ionizing radiation.
More recently, a central theme of our research has been to provide experimental evidence that such
clusters of DNA lesions are indeed formed in mammalian cells and as a consequence they compromise
the ability of the cellular repair machinery to recognize and process them. Evidence indicates that delayed
repair of clustered DNA damage may lead to the formation of mutations, chromosomal aberrations and
genetic instability. The research area is still in its infancy, although emerging evidence indicates that
clustered damage sites may contribute, in part, to understanding the basis of low dose health effects of
radiation. As we approach the end of our journey I will focus on the spatiotemporal dynamics of the DNA
damage/repair processes which complements the extensive biochemical knowledge on the repair of
radiation-induced lesions including DNA double strand breaks. To date, biological thinking has tended to
predominate in understanding DNA damage repair pathways however knowledge of recruitment of
proteins in real time to DNA damage have opened up novel thinking . I hope I will have stimulated your
thinking by showing some examples on how DNA damage/repair does depend on the right chemistry.
4 | P a g e
