Mechanisms of Ubiquitin-Nucleosome Recognition and Regulation of 53BP1 Chromatin Recruitment by RNF168/169 and RAD18

Molecular Cell
Qi HuGeorges Mer

Abstract

The protein 53BP1 plays a central regulatory role in DNA double-strand break repair. 53BP1 relocates to chromatin by recognizing RNF168-mediated mono-ubiquitylation of histone H2A Lys15 in the nucleosome core particle dimethylated at histone H4 Lys20 (NCP-ubme). 53BP1 relocation is terminated by ubiquitin ligases RNF169 and RAD18 via unknown mechanisms. Using nuclear magnetic resonance (NMR) spectroscopy and biochemistry, we show that RNF169 bridges ubiquitin and histone surfaces, stabilizing a pre-existing ubiquitin orientation in NCP-ubme to form a high-affinity complex. This conformational selection mechanism contrasts with the low-affinity binding mode of 53BP1, and it ensures 53BP1 displacement by RNF169 from NCP-ubme. We also show that RAD18 binds tightly to NCP-ubme through a ubiquitin-binding domain that contacts ubiquitin and nucleosome surfaces accessed by 53BP1. Our work uncovers diverse ubiquitin recognition mechanisms in the nucleosome, explaining how RNF168, RNF169, and RAD18 regulate 53BP1 chromatin recruitment and how specificity can be achieved in the recognition of a ubiquitin-modified substrate.

References

Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Jun 18, 1999·Methods in Enzymology·K LugerT J Richmond
Nov 15, 2000·Quarterly Reviews of Biophysics·A E Ferentz, G Wagner
Sep 8, 2001·Journal of Molecular Biology·M V BotuyanC H Arrowsmith
May 26, 2004·The Journal of Cell Biology·Irene M WardJunjie Chen
Jul 10, 2004·Structure·Maria Victoria E BotuyanGeorges Mer
Feb 8, 2006·Nature Structural & Molecular Biology·Sangho LeeJames H Hurley
Nov 7, 2006·Journal of Magnetic Resonance·Junji IwaharaG Marius Clore
Feb 21, 2009·Nucleic Acids Research·Kenji WatanabeSatoshi Tateishi
Apr 28, 2009·Nature Cell Biology·Jun HuangJunjie Chen
Oct 21, 2009·Nature Chemical Biology·David D BoehrPeter E Wright
May 11, 2010·Nature Structural & Molecular Biology·Peter BouwmanJos Jonkers
May 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Hiroaki TachiwanaHitoshi Kurumizaka
Jul 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Hidenori KatoYawen Bai
Jul 21, 2011·Analytical Biochemistry·Christopher E Berndsen, Cynthia Wolberger
Jul 21, 2011·The EMBO Journal·Matthew L BentleyAndrea G Cochran
Mar 3, 2012·Nature·Anthony A ArmstrongChristopher D Lima
Apr 12, 2012·The Journal of Cell Biology·Maria PoulsenNiels Mailand
Jun 27, 2012·The Journal of Biological Chemistry·Jie ChenMichael S Y Huen
Sep 1, 1994·Journal of Biomolecular NMR·B A Johnson, R A Blevins
Sep 18, 2012·Cell·Francesca MattiroliTitia K Sixma
Sep 20, 2012·The Journal of Biological Chemistry·Richard G Hibbert, Titia K Sixma
Dec 12, 2012·Journal of Biomolecular NMR·Yoshikazu HattoriChojiro Kojima
Dec 21, 2012·Cell Cycle·Xiaoqin ZhangJianye Zang
Mar 19, 2013·Annual Review of Biophysics·Robert P Rambo, John A Tainer

❮ Previous
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Citations

Dec 1, 2017·Nucleic Acids Research·Xiang GuoJiadong Wang
Feb 8, 2018·The Journal of Biological Chemistry·Joonyoung Her, Samuel F Bunting
Aug 30, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Marcus D Wilson, Daniel Durocher
Jun 23, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Rajivgandhi Sundaram, Dileep Vasudevan
Sep 11, 2019·Proceedings of the National Academy of Sciences of the United States of America·Justine SitzAmélie Fradet-Turcotte
Aug 1, 2019·Nature Communications·Tarun S NambiarAlberto Ciccia
May 20, 2020·Nature Communications·Jessica L KelliherJustin W C Leung
Aug 15, 2018·Proceedings of the National Academy of Sciences of the United States of America·Liwei AnMichael S Y Huen
Jul 4, 2018·Nature Structural & Molecular Biology·Maria Victoria BotuyanGeorges Mer
Feb 20, 2020·Cell & Bioscience·Jia YuZhenkun Lou
Apr 17, 2019·Nature Communications·Velten HornHugo van Ingen
Jul 14, 2020·Nucleic Acids Research·Aleksandra SkrajnaRobert K McGinty
Jun 24, 2020·Cancers·Barbara N BorsosTibor Pankotai
Mar 28, 2020·Cancer Research·John J KraisNeil Johnson
Nov 19, 2020·Molecular & Cellular Proteomics : MCP·Congcong LuBenjamin A Garcia
Feb 12, 2021·The Journal of Cell Biology·Carolina Dos Santos PassosRobert E Cohen
Jan 25, 2021·Trends in Genetics : TIG·Francesca Mattiroli, Lorenza Penengo
Oct 7, 2020·Molecular Cell·Franziska WalserLorenza Penengo
Dec 15, 2020·Trends in Biochemical Sciences·Robert M VaughanScott B Rothbart
Oct 28, 2019·Molecular Cell·Elsa CallenAndré Nussenzweig
Apr 3, 2021·The FEBS Journal·Jessica KelliherJustin Wai Chung Leung
May 15, 2021·DNA Repair·Mengfan TangJunjie Chen
Jun 19, 2021·Computational and Structural Biotechnology Journal·Junrui ZhangStefan T Arold
Jul 30, 2021·Nature·Jordan R BeckerJ Ross Chapman
Feb 14, 2019·Journal of the American Chemical Society·Guo-Chao ChuLei Liu
Mar 1, 2019·ACS Chemical Biology·Catherine A Musselman, Tatiana G Kutateladze
Jan 29, 2021·Journal of Biochemistry·Md Kawsar MustofaSatoshi Tateishi
Sep 11, 2021·Journal of Molecular Biology·Weibin GongYingang Feng

❮ Previous
Next ❯

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