Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase Complex

Zhang, Heng; Devoucoux, Maëva; Song, Xiaosheng; Li, Li; Ayaz, Gamze; Cheng, Harry; Tempel, Wolfram; Dong, Cheng; Loppnau, Peter; Côté, Jacques; Min, Jinrong

doi:10.1016/j.celrep.2020.03.003

Title: Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase Complex

Journal Article · Tue Mar 24 00:00:00 EDT 2020 · Cell Reports

DOI:https://doi.org/10.1016/j.celrep.2020.03.003· OSTI ID:1838539

Zhang, Heng ^[1]; Devoucoux, Maëva ^[2]; Song, Xiaosheng ^[1]; Li, Li ^[1]; Ayaz, Gamze ^[3]; Cheng, Harry ^[1]; Tempel, Wolfram ^[1]; Dong, Cheng ^[1]; Loppnau, Peter ^[1]; Côté, Jacques ^[2]; Min, Jinrong ^[4]

Univ. of Toronto, ON (Canada). Structural Genomics Consortium
CHU de Québec-Université Laval Research Center, Quebec City, QC (Canada). Laval University Cancer Research Center
Univ. of Toronto, ON (Canada). Structural Genomics Consortium; Middle East Technical Univ., Ankara (Turkey)
Central China Normal Univ., Wuhan (China). Hubei Key Laboratory of Genetic Regulation and Integrative Biology; Univ. of Toronto, ON (Canada). Structural Genomics Consortium

MBTD1, a H4K20me reader, has recently been identified as a component of the NuA4/TIP60 acetyltransferase complex, regulating gene expression and DNA repair. NuA4/TIP60 inhibits 53BP1 binding to chromatin through recognition of the H4K20me mark by MBTD1 and acetylation of H2AK15, blocking the ubiquitination mark required for 53BP1 localization at DNA breaks. The NuA4/TIP60 non-catalytic subunit EPC1 enlists MBTD1 into the complex, but the detailed molecular mechanism remains incompletely explored. Here, we present the crystal structure of the MBTD1-EPC1 complex, revealing a hydrophobic C-terminal fragment of EPC1 engaging the MBT repeats of MBTD1 in a site distinct from the H4K20me binding site. Different cellular assays validate the physiological significance of the key residues involved in the MBTD1-EPC1 interaction. Our study provides a structural framework for understanding the mechanism by which MBTD1 recruits the NuA4/TIP60 acetyltransferase complex to influence transcription and DNA repair pathway choice.

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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC); Natural Sciences and Engineering Research Council of Canada (NSERC); Innovative Medicines Initiative; Canadian Institutes of Health Research

Grant/Contract Number:: FDN-143314; RGPIN-2016-06300; 115766

OSTI ID:: 1838539

Journal Information:: Cell Reports, Vol. 30, Issue 12; ISSN 2211-1247

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (33)

Spatiotemporal regulation of posttranslational modifications in the DNA damage response Dantuma, Nico P.; Attikum, Haico The EMBO Journal, Vol. 35, Issue 1 https://doi.org/10.15252/embj.201592595	journal	December 2015
53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark Fradet-Turcotte, Amélie; Canny, Marella D.; Escribano-Díaz, Cristina Nature, Vol. 499, Issue 7456 https://doi.org/10.1038/nature12318	journal	June 2013
Enhancer of Polycomb1, a Novel Homeodomain Only Protein-binding Partner, Induces Skeletal Muscle Differentiation Kee, Hae Jin; Kim, Ju-Ryoung; Nam, Kwang-Il Journal of Biological Chemistry, Vol. 282, Issue 10 https://doi.org/10.1074/jbc.M611198200	journal	March 2007
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
Playing the End Game: DNA Double-Strand Break Repair Pathway Choice Chapman, J. Ross; Taylor, Martin R. G.; Boulton, Simon J. Molecular Cell, Vol. 47, Issue 4 https://doi.org/10.1016/j.molcel.2012.07.029	journal	August 2012
Role for O-Glycosylation of RFP in the Interaction with Enhancer of Polycomb Tezel, Gaye; Shimono, Yohei; Murakumo, Yoshiki Biochemical and Biophysical Research Communications, Vol. 290, Issue 1 https://doi.org/10.1006/bbrc.2001.6161	journal	January 2002
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
REFMAC 5 for the refinement of macromolecular crystal structures Murshudov, Garib N.; Skubák, Pavol; Lebedev, Andrey A. Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444911001314	journal	March 2011
DNA End Resection: Facts and Mechanisms Liu, Ting; Huang, Jun Genomics, Proteomics & Bioinformatics, Vol. 14, Issue 3 https://doi.org/10.1016/j.gpb.2016.05.002	journal	June 2016
Studying post-translational modifications with protein interaction networks Woodsmith, Jonathan; Stelzl, Ulrich Current Opinion in Structural Biology, Vol. 24 https://doi.org/10.1016/j.sbi.2013.11.009	journal	February 2014
Dual Coordination of Post Translational Modifications in Human Protein Networks Woodsmith, Jonathan; Kamburov, Atanas; Stelzl, Ulrich PLoS Computational Biology, Vol. 9, Issue 3 https://doi.org/10.1371/journal.pcbi.1002933	journal	March 2013
A Scalable Genome-Editing-Based Approach for Mapping Multiprotein Complexes in Human Cells Dalvai, Mathieu; Loehr, Jeremy; Jacquet, Karine Cell Reports, Vol. 13, Issue 3 https://doi.org/10.1016/j.celrep.2015.09.009	journal	October 2015
Expanding and reprogramming the genetic code Chin, Jason W. Nature, Vol. 550, Issue 7674 https://doi.org/10.1038/nature24031	journal	October 2017
The tale of a tail: histone H4 acetylation and the repair of DNA breaks Dhar, Surbhi; Gursoy-Yuzugullu, Ozge; Parasuram, Ramya Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 372, Issue 1731 https://doi.org/10.1098/rstb.2016.0284	journal	August 2017
Structural Studies of a Four-MBT Repeat Protein MBTD1 Eryilmaz, Jitka; Pan, Patricia; Amaya, Maria F. PLoS ONE, Vol. 4, Issue 10 https://doi.org/10.1371/journal.pone.0007274	journal	October 2009
How good are my data and what is the resolution? Evans, Philip R.; Murshudov, Garib N. Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 7 https://doi.org/10.1107/S0907444913000061	journal	June 2013
Epigenetic Modifications in Double-Strand Break DNA Damage Signaling and Repair Rossetto, Dorine; Truman, Andrew W.; Kron, Stephen J. Clinical Cancer Research, Vol. 16, Issue 18 https://doi.org/10.1158/1078-0432.CCR-10-0513	journal	September 2010
Reading chromatin signatures after DNA double-strand breaks Wilson, Marcus D.; Durocher, Daniel Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 372, Issue 1731 https://doi.org/10.1098/rstb.2016.0280	journal	August 2017
The control of DNA repair by the cell cycle Hustedt, Nicole; Durocher, Daniel Nature Cell Biology, Vol. 19, Issue 1 https://doi.org/10.1038/ncb3452	journal	December 2016
Solution structure of the FCS zinc finger domain of the human polycomb group protein L(3)mbt-like 2: Structure of the FCS Zinc Finger Domain Lechtenberg, Bernhard C.; Allen, Mark D.; Rutherford, Trevor J. Protein Science, Vol. 18, Issue 3 https://doi.org/10.1002/pro.51	journal	January 2009
Introduction to the Thematic Minireview Series: DNA double-strand break repair and pathway choice Sung, Patrick Journal of Biological Chemistry, Vol. 293, Issue 27 https://doi.org/10.1074/jbc.TM118.003212	journal	July 2018
Acetylation limits 53BP1 association with damaged chromatin to promote homologous recombination Tang, Jiangbo; Cho, Nam Woo; Cui, Gaofeng Nature Structural & Molecular Biology, Vol. 20, Issue 3 https://doi.org/10.1038/nsmb.2499	journal	February 2013
DNA repair pathway choice at various conditions immediately post irradiation Liu, Min; Wang, Hongyan; Lee, Solah International Journal of Radiation Biology, Vol. 92, Issue 12 https://doi.org/10.1080/09553002.2016.1230243	journal	October 2016
Roles of eukaryotic topoisomerases in transcription, replication and genomic stability Pommier, Yves; Sun, Yilun; Huang, Shar-yin N. Nature Reviews Molecular Cell Biology, Vol. 17, Issue 11 https://doi.org/10.1038/nrm.2016.111	journal	September 2016
SFMBT2 (Scm-like with four mbt domains 2) negatively regulates cell migration and invasion in prostate cancer cells Gwak, Jungsug; Shin, Jee Yoon; Lee, Kwanghyun Oncotarget, Vol. 7, Issue 30 https://doi.org/10.18632/oncotarget.10198	journal	June 2016
The TIP60 Complex Regulates Bivalent Chromatin Recognition by 53BP1 through Direct H4K20me Binding and H2AK15 Acetylation Jacquet, Karine; Fradet-Turcotte, Amélie; Avvakumov, Nikita Molecular Cell, Vol. 62, Issue 3 https://doi.org/10.1016/j.molcel.2016.03.031	journal	May 2016
Structural basis for targeting the chromatin repressor Sfmbt to Polycomb response elements Alfieri, Claudio; Gambetta, Maria Cristina; Matos, Raquel Genes & Development, Vol. 27, Issue 21 https://doi.org/10.1101/gad.226621.113	journal	November 2013
Role of 53BP1 in the Regulation of DNA Double-Strand Break Repair Pathway Choice Gupta, Arun; Hunt, Clayton R.; Chakraborty, Sharmistha Radiation Research, Vol. 181, Issue 1 https://doi.org/10.1667/RR13572.1	journal	January 2014
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
53BP1: pro choice in DNA repair Zimmermann, Michal; de Lange, Titia Trends in Cell Biology, Vol. 24, Issue 2 https://doi.org/10.1016/j.tcb.2013.09.003	journal	February 2014
Prime, Repair, Restore: The Active Role of Chromatin in the DNA Damage Response Soria, Gaston; Polo, Sophie E.; Almouzni, Geneviève Molecular Cell, Vol. 46, Issue 6 https://doi.org/10.1016/j.molcel.2012.06.002	journal	June 2012
Understanding the Histone DNA Repair Code: H4K20me2 Makes Its Mark Paquin, Karissa L.; Howlett, Niall G. Molecular Cancer Research, Vol. 16, Issue 9 https://doi.org/10.1158/1541-7786.MCR-17-0688	journal	June 2018
Crosstalk of DNA double‐strand break repair pathways in poly(ADP‐ribose) polymerase inhibitor treatment of breast cancer susceptibility gene 1/2‐mutated cancer Sunada, Shigeaki; Nakanishi, Akira; Miki, Yoshio Cancer Science, Vol. 109, Issue 4 https://doi.org/10.1111/cas.13530	journal	March 2018

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59 BASIC BIOLOGICAL SCIENCES
MBTD1
EPC1
NuA4
TIP60
H4K20me
DNA repair
crystal structure

Title: Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase Complex

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