Studies in radiation damage to DNA and its component biomolecules LSI Fellowship Dr Sylwia Ptasinska

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Ionizing radiation can produce a range of different types of damage to DNA, the molecule that underpins all life. DNA is shaped as a helix and may be broken in one of two different ways; double strand breaks (dsb), where both strands of the helix are broken and single-strand breaks (ssb) where only one strand of the helix is broken. Double strand breaks are the more dangerous since they can lead to lasting damage, including mutations and ultimately cell death. It is now known that the effect of different types of radiation (alpha particles, x-rays, gamma rays) is critically dependent on the patterns of ionizations they produce on a microscopic scale, comparable with the diameter of the DNA helix (nanometers). Furthermore we now know that that much of the radiation damage is site specific, i.e. targeted on specific molecular sub blocks of the larger DNA molecule. Hence in order to understand the mechanisms of radiation damage it is essential to understand the interaction of different types of radiation with the constituent cellular molecules (DNA itself and its components - the nucleotides, the nucleosides, phosphates, sugars and, of course, cellular water).The basic mechanisms by which DNA damage is thought to occur has recently been brought into question by new studies of electron interactions with DNA and its constituent molecules. Strand breaks in DNA may be initiated by low energy electrons attacking directly DNA's molecular constituents identity, Thus radiation damage may be described at an individual molecule level. Such a molecular picture may be used to explain the well known correlation between electron attachment rates of many molecules and their carcinogenicity (ability to induce cancer) and may be used to suggest new compounds to be adopted in radiation therapy as treatment enhancing sensitizers.I wish to develop my studies of electron interactions with molecular components of DNA to study the effect of radiation of DNA itself. I want to explore/identify patterns in the electron induced molecular fragmentation with strand breaks in DNA and then extend my studies to explore radiation damage in the cell itself.