Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Natural variation in the freezing tolerance of Arabidopsis thaliana: Effects of RNAi-induced CBF depletion and QTL localisation vary among accessions

Plants from temperate regions are able to withstand freezing temperatures and to increase their freezing tolerance during exposure to low, but non-freezing, temperatures through a process known as cold acclimation. Key regulatory proteins in this process are the cold-induced CBF1, 2 and 3 transcription factors which control many cold regulated genes. Although much work has focused on this signal transduction pathway, the details of its regulation and of its quantitative contribution to cold acclimation are still unclear. Here, we have used the large natural variation present in the 48 accessions of the Versailles core collection of Arabidopsis thaliana to further elucidate the function of the CBF transcription factors. CBF gene expression studies showed that the freezing sensitive accessions had mostly low expression levels 2 h after transfer of plants to 5 degrees C, while the most tolerant accessions showed a wide range of CBF expression levels. To investigate the quantitative contribution of CBF expression to plant freezing tolerance and low temperature growth performance. RNAi lines targeting all three CBF genes were produced in eight different accessions. We observed striking differences between different accessions in the effects that reduced CBF expression had on freezing tolerance, while effects on growth were generally too small to draw firm conclusions. Analysis of CBF expression indicated a tight co-regulation between CBF1 and CBF3, while the relationship between the expression levels of CBF2 and CBF1 or CBF3 strongly depended on the genetic background of the RNAi lines. In agreement with the observed differences between the different accessions, QTL analyses with two different RIL populations indicated that QTL localisation varies strongly between populations. Collectively, these results show that both the regulation of the CBF genes and their relative contribution to freezing tolerance strongly depend on the accession studied. In addition, natural variation is suggested to be an interesting source of novel regulatory pathways and genes that may be useful in the future for improving plant freezing tolerance. (C) 2010 Elsevier Ireland Ltd. All rights reserved