Spatiotemporal dynamics of 53BP1 dimer recruitment to a DNA double strand break

Jieqiong Lou; David G Priest; Ashleigh Solano; Adele Kerjouan; Elizabeth Hinde

Journal article

Spatiotemporal dynamics of 53BP1 dimer recruitment to a DNA double strand break

Jieqiong Lou, David G Priest, Ashleigh Solano, Adele Kerjouan, Elizabeth Hinde

Nature Communications | Nature Research | Published : 2020

DOI: 10.1038/s41467-020-19504-3

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Abstract

Tumor suppressor p53-binding protein 1 (53BP1) is a DNA repair protein essential for the detection, assessment, and resolution of DNA double strand breaks (DSBs). The presence of a DSB is signaled to 53BP1 via a local histone modification cascade that triggers the binding of 53BP1 dimers to chromatin flanking this type of lesion. While biochemical studies have established that 53BP1 exists as a dimer, it has never been shown in a living cell when or where 53BP1 dimerizes upon recruitment to a DSB site, or upon arrival at this nuclear location, how the DSB histone code to which 53BP1 dimers bind regulates retention and self-association into higher-order oligomers. Thus, here in live-cell nucl..

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University of Melbourne Researchers

Elizabeth Hinde Author Physics

Jieqiong Lou Author Physics

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Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)

Awarded by Australian Research Council (ARC)

Awarded by Australian NHMRC

Awarded by Australian NHMRC Career Development Fellowship

Funding Acknowledgements

We thank Dr. Gaelle Legube and Dr. Thomas Clouaire for providing the DSB inducible via AsiSI cell system (DIvA). We thank Professor Thanos D. Halazonetis for kindly providing 53BP1 mutant plasmids. We thank Professor Enrico Gratton for useful discussion on data analysis. We thank Jee Khor for useful discussion on sample preparation. J.L. is supported by an Australian National Health and Medical Research Council (NHMRC) project grant (APP1104461) and Albert Shimmins Research Continuity Funding. D.P. is supported by an Australian Research Council (ARC) discovery project (DP180101387). A.K. is supported by an Australian NHMRC project grant (APP1121907). E.H. is supported by an Australian NHMRC Career Development Fellowship (APP1124762) and the Jacob Haimson Beverly Mecklenburg Lectureship. We thank the Biological Optical Microscopy Platform, University of Melbourne, for enabling access to the Olympus FV3000 confocal laser scanning microscope.