Poster Presentation 2019 Hunter Cell Biology Meeting

Histone FLIM-FRET microscopy identifies ATM- and RNF8- dependent rearrangement of chromatin architecture during the DNA damage response (#123)

Jieqiong Lou 1 2 , Tony Cesare 3 , Elizabeth Hinde 2
  1. University of Melbourne, Melbourne, VICTORIA, Australia
  2. Biochemistry and Molecular Biology Department, University of Melbourne, Melbourne, VIC, Australia
  3. Genomic Integrity Group, Children’s Medical Research Institute, Westmead, NSW, Australia

To investigate how chromatin architecture is spatiotemporally organised at a double strand break (DSB) repair locus, we established a biophysical method to quantify chromatin compaction at the nucleosome level during the DNA damage response (DDR). The method is based on phasor image correlation spectroscopy (ICS) of histone FLIM-FRET microscopy data acquired in live cells co-expressing H2B-eGFP and H2B-mCherry. This multiplexed approach generates spatiotemporal maps of nuclear-wide chromatin compaction that when coupled with laser micro-irradiation, are capable of quantifying the size, stability, and spacing between compact chromatin foci throughout the DDR. Using this technology, we identify that ATM and RNF8 regulate rapid chromatin decompaction at DSBs and formation of a compact chromatin ring surrounding the repair locus. This chromatin architecture serves to demarcate the repair locus from the surrounding nuclear environment and modulate 53BP1 mobility.