Defining the molecular link between DNA repair and chromatin remodelling

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This study investigates how plants detect, signal and repair DNA damage. DNA is essential for growth and reproduction but is constantly being damaged by highly reactive chemicals present in the cell and environmental factors including carcinogens, UVB and soil pollutants such as heavy metals. A single DNA double strand break is sufficient to cause cell death and DNA therefore needs to be continuously repaired if the organism is to survive. The first steps in repair are detection and signalling of DNA damage. It is important that the cell rapidly recognises and signals the presence of DNA damage to minimise the harmful effects on growth and development of the organism. In this study, to be undertaken at the Faculty of Biological Sciences, University of Leeds, we will establish how DNA double strand breaks are detected and repaired using the model plant Arabidopsis thaliana. We will build on our existing knowledge of DNA damage and repair in plants, including exciting recent results that show that the primary detector of DNA damage, termed the MRN complex, interacts with proteins responsible for the modification of histones (proteins that package DNA and regulate its accessibility). This novel result suggests a mechanism by which the cell can signal DNA damage by modifying histones at the site of the break in the very early stages of DNA damage detection and repair. In this proposal, we will test this hypothesis that histone modification plays a crucial early role in DNA repair. We have isolated mutant plants lacking our newly identified histone modifying proteins, and in this study we will see if DNA breaks are processed differently, in terms of histone modification, the rate of repair and the 'unpacking' of DNA. We will also determine the effects of these mutations on the ability of plants to withstand DNA damage. It is important that we understand these signalling processes in plants, as DNA damage signalling and repair is required to allow growth of crop plants in conditions of environmental stress, and failure of these pathways will result in reduced yields and the accumulation of deleterious mutations in future generations. In view of climate change, it is now important that we understand how plants respond to environmental stresses, which will impact on crop survival and yield. As many of the processes are conserved amongst different organisms, these studies may also have important implications for cancer, aging and gene therapy.