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

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 chromati...

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Autores principales: Lou, Jieqiong, Priest, David G., Solano, Ashleigh, Kerjouan, Adèle, Hinde, Elizabeth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666136/
https://www.ncbi.nlm.nih.gov/pubmed/33188174
http://dx.doi.org/10.1038/s41467-020-19504-3
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author Lou, Jieqiong
Priest, David G.
Solano, Ashleigh
Kerjouan, Adèle
Hinde, Elizabeth
author_facet Lou, Jieqiong
Priest, David G.
Solano, Ashleigh
Kerjouan, Adèle
Hinde, Elizabeth
author_sort Lou, Jieqiong
collection PubMed
description 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 nuclear architecture we quantify the spatiotemporal dynamics of 53BP1 oligomerization during a DSB DNA damage response by coupling fluorescence fluctuation spectroscopy (FFS) with the DSB inducible via AsiSI cell system (DIvA). From adopting this multiplexed approach, we find that preformed 53BP1 dimers relocate from the nucleoplasm to DSB sites, where consecutive recognition of ubiquitinated lysine 15 of histone 2A (H2AK15ub) and di-methylated lysine 20 of histone 4 (H4K20me2), leads to the assembly of 53BP1 oligomers and a mature 53BP1 foci structure.
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spelling pubmed-76661362020-11-17 Spatiotemporal dynamics of 53BP1 dimer recruitment to a DNA double strand break Lou, Jieqiong Priest, David G. Solano, Ashleigh Kerjouan, Adèle Hinde, Elizabeth Nat Commun Article 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 nuclear architecture we quantify the spatiotemporal dynamics of 53BP1 oligomerization during a DSB DNA damage response by coupling fluorescence fluctuation spectroscopy (FFS) with the DSB inducible via AsiSI cell system (DIvA). From adopting this multiplexed approach, we find that preformed 53BP1 dimers relocate from the nucleoplasm to DSB sites, where consecutive recognition of ubiquitinated lysine 15 of histone 2A (H2AK15ub) and di-methylated lysine 20 of histone 4 (H4K20me2), leads to the assembly of 53BP1 oligomers and a mature 53BP1 foci structure. Nature Publishing Group UK 2020-11-13 /pmc/articles/PMC7666136/ /pubmed/33188174 http://dx.doi.org/10.1038/s41467-020-19504-3 Text en © Crown 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lou, Jieqiong
Priest, David G.
Solano, Ashleigh
Kerjouan, Adèle
Hinde, Elizabeth
Spatiotemporal dynamics of 53BP1 dimer recruitment to a DNA double strand break
title Spatiotemporal dynamics of 53BP1 dimer recruitment to a DNA double strand break
title_full Spatiotemporal dynamics of 53BP1 dimer recruitment to a DNA double strand break
title_fullStr Spatiotemporal dynamics of 53BP1 dimer recruitment to a DNA double strand break
title_full_unstemmed Spatiotemporal dynamics of 53BP1 dimer recruitment to a DNA double strand break
title_short Spatiotemporal dynamics of 53BP1 dimer recruitment to a DNA double strand break
title_sort spatiotemporal dynamics of 53bp1 dimer recruitment to a dna double strand break
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666136/
https://www.ncbi.nlm.nih.gov/pubmed/33188174
http://dx.doi.org/10.1038/s41467-020-19504-3
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