Role of chromatin dynamics during the DNA damage response
Tumour suppression relies on the preservation of genome integrity and this is maintained by a cellular surveillance system called the DNA damage response (DDR). Amazingly the DDR can almost instantaneously detect a genomic lesion. However, how it spatiotemporally coordinates DNA repair factor recruitment to that damage site is not currently understood. We recently demonstrated that double-strand breaks (DSB) induce a transient local ‘opening’ of chromatin at the damage site that is bordered by an increased level of chromatin compaction (Hinde et al. 2014 Biophys. J 107(1)). These dynamic rearrangements in local DNA density appear to facilitate DNA repair factor accumulation at only the damage site. The overall aim of this project is to investigate how these changes in chromatin compaction modulate genome topology to facilitate the DDR. By use of a fluorescence lifetime imaging microscopy (FLIM) based assay, we will test the hypothesis that spatial heterogeneity in chromatin compaction during the DDR serves to facilitate DNA repair factor access whilst blocking transcription of neighbouring genes.
Jieqiong Lou, Post doctoral researcher
Jee Khor, Honours research student
Dr Tony Cesare, Childrens Medical Research Institute, Sydney, Australia
Professor Enrico Gratton, University of California, Irvine, USA
NHMRC Project Grant (2016-2019) 'The role of nuclear architecture in the DNA damage response'.
Hinde E, Kong X, Yokomori K, Gratton E. Chromatin dynamics during DNA repair revealed by pair correlation analysis of molecular flow. Biophysical Journal 2014; 107(1): 55-65.
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