Einzeltreffer — DigiBib

The chromatin remodeler ALC1 is recruited to and activated by DNA damage-induced poly(ADP-ribose) (PAR) chains deposited by PARP1/PARP2/HPF1 upon detection of DNA lesions. ALC1 has emerged as a candidate drug target for cancer therapy as its loss confers synthetic lethality in homologous recombination-deficient cells. However, structure-based drug design and molecular analysis of ALC1 have been hindered by the requirement for PARylation and the highly heterogeneous nature of this post-translational modification. Here, we reconstituted an ALC1 and PARylated nucleosome complex modified in vitro using PARP2 and HPF1. This complex was amenable to cryo-EM structure determination without cross-linking, which enabled visualization of several intermediate states of ALC1 from the recognition of the PARylated nucleosome to the tight binding and activation of the remodeler. Functional biochemical assays with PARylated nucleosomes highlight the importance of nucleosomal epitopes for productive remodeling and suggest that ALC1 preferentially slides nucleosomes away from DNA breaks.

Competing Interests: LB, GG, AS, LL, KB, DD, MH, GH none, SB is co-founder and VP Science Strategy at Artios Pharma Ltd, SD Reviewing editor, eLife

Titel:	Structure and dynamics of the chromatin remodeler ALC1 bound to a PARylated nucleosome.
Autor/in / Beteiligte Person:	Bacic, L ; Gaullier, G ; Sabantsev, A ; Lehmann, LC ; Brackmann, K ; Dimakou, D ; Halic, M ; Hewitt, G ; Boulton, SJ ; Deindl, S
Link:	Full Text Finder (Volltext)
Zeitschrift:	ELife, Jg. 10 (2021-09-06)
Veröffentlichung:	Cambridge, UK : eLife Sciences Publications, Ltd., 2012-, 2021
Medientyp:	academicJournal
ISSN:	2050-084X (electronic)
DOI:	10.7554/eLife.71420
Schlagwort:	Carrier Proteins genetics Cryoelectron Microscopy DNA Helicases genetics DNA Helicases ultrastructure DNA-Binding Proteins genetics DNA-Binding Proteins ultrastructure Humans Kinetics Models, Molecular Nuclear Proteins genetics Nucleosomes genetics Nucleosomes ultrastructure Poly (ADP-Ribose) Polymerase-1 genetics Poly(ADP-ribose) Polymerases genetics Protein Binding Protein Conformation Recombinant Proteins metabolism Structure-Activity Relationship Substrate Specificity Carrier Proteins metabolism Chromatin Assembly and Disassembly DNA Helicases metabolism DNA-Binding Proteins metabolism Nuclear Proteins metabolism Nucleosomes metabolism Poly (ADP-Ribose) Polymerase-1 metabolism Poly ADP Ribosylation Poly(ADP-ribose) Polymerases metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Video-Audio Media Language: English [Elife] 2021 Sep 06; Vol. 10. <i>Date of Electronic Publication: </i>2021 Sep 06. MeSH Terms: Chromatin Assembly and Disassembly* ; Poly ADP Ribosylation* ; Carrier Proteins / metabolism ; DNA Helicases / metabolism ; DNA-Binding Proteins / metabolism ; Nuclear Proteins / metabolism ; Nucleosomes / metabolism ; Poly (ADP-Ribose) Polymerase-1 / metabolism ; Poly(ADP-ribose) Polymerases / *metabolism ; Carrier Proteins / genetics ; Cryoelectron Microscopy ; DNA Helicases / genetics ; DNA Helicases / ultrastructure ; DNA-Binding Proteins / genetics ; DNA-Binding Proteins / ultrastructure ; Humans ; Kinetics ; Models, Molecular ; Nuclear Proteins / genetics ; Nucleosomes / genetics ; Nucleosomes / ultrastructure ; Poly (ADP-Ribose) Polymerase-1 / genetics ; Poly(ADP-ribose) Polymerases / genetics ; Protein Binding ; Protein Conformation ; Recombinant Proteins / metabolism ; Structure-Activity Relationship ; Substrate Specificity References: Science. 2018 Oct 12;362(6411):. (PMID: 30309918) ; Cell. 2019 Mar 7;176(6):1490-1501.e12. (PMID: 30765112) ; Mol Cell. 2020 Dec 3;80(5):862-875.e6. (PMID: 33275888) ; Elife. 2020 Jun 16;9:. (PMID: 32543371) ; Methods Mol Biol. 2017;1608:431-444. (PMID: 28695525) ; Cell Res. 2019 Apr;29(4):330-333. (PMID: 30770869) ; Mol Cell. 2017 Dec 7;68(5):847-859.e7. (PMID: 29220652) ; Nat Methods. 2019 Nov;16(11):1153-1160. (PMID: 31591578) ; FEBS J. 2021 Jul 29;:. (PMID: 34323016) ; Elife. 2019 Jun 18;8:. (PMID: 31210637) ; Mol Cell. 2019 Dec 5;76(5):712-723.e4. (PMID: 31733991) ; Science. 2019 Nov 15;366(6467):838-843. (PMID: 31672915) ; Nucleic Acids Res. 2018 Dec 14;46(22):12154-12165. (PMID: 30321391) ; Nat Commun. 2021 Jul 1;12(1):4057. (PMID: 34210977) ; Science. 2016 Feb 12;351(6274):725-8. (PMID: 26912860) ; Nat Struct Mol Biol. 2006 Apr;13(4):339-46. (PMID: 16518397) ; Mol Cell. 2021 Feb 18;81(4):767-783.e11. (PMID: 33333017) ; J Struct Biol. 2015 Nov;192(2):216-21. (PMID: 26278980) ; Curr Opin Struct Biol. 2021 Dec;71:16-26. (PMID: 34198054) ; Nat Methods. 2017 Mar;14(3):290-296. (PMID: 28165473) ; Nature. 2018 Apr;556(7701):391-395. (PMID: 29643506) ; Nat Struct Mol Biol. 2013 Sep;20(9):1116-8. (PMID: 23934152) ; Elife. 2017 Jan 21;6:. (PMID: 28109157) ; Nature. 2020 Jan;577(7792):717-720. (PMID: 31969703) ; Mol Biol Cell. 2016 Dec 1;27(24):3791-3799. (PMID: 27733626) ; Nature. 2020 Mar;579(7799):452-455. (PMID: 32188938) ; Elife. 2021 Dec 07;10:. (PMID: 34874266) ; J Biol Chem. 2012 Dec 21;287(52):43527-32. (PMID: 23132853) ; Nature. 2020 Sep;585(7826):609-613. (PMID: 32939087) ; Science. 2009 Sep 4;325(5945):1240-3. (PMID: 19661379) ; Science. 2021 Jan 22;371(6527):. (PMID: 33479126) ; PLoS One. 2020 Nov 3;15(11):e0240932. (PMID: 33141820) ; Methods Enzymol. 2004;375:23-44. (PMID: 14870657) ; Nature. 2017 Oct 26;550(7677):539-542. (PMID: 29019976) ; Elife. 2020 Jan 10;9:. (PMID: 31922488) ; Acta Crystallogr D Struct Biol. 2018 Jun 1;74(Pt 6):531-544. (PMID: 29872004) ; Nat Struct Mol Biol. 2019 Apr;26(4):258-266. (PMID: 30872815) ; Cell Rep. 2019 Feb 12;26(7):1681-1690.e5. (PMID: 30759380) ; Science. 2011 Nov 18;334(6058):977-82. (PMID: 22096199) ; Nature. 2016 Aug 4;536(7614):100-3. (PMID: 27462807) ; Nature. 2017 Apr 27;544(7651):440-445. (PMID: 28424519) ; Nat Commun. 2021 Nov 18;12(1):6675. (PMID: 34795260) ; Methods Enzymol. 1988;156:116-9. (PMID: 2835597) ; Science. 2020 Feb 21;367(6480):875-881. (PMID: 32001526) ; Nucleic Acids Res. 2019 Sep 26;47(17):9400-9409. (PMID: 31402386) ; Nat Methods. 2021 Feb;18(2):176-185. (PMID: 33542510) ; Nat Struct Mol Biol. 2013 Sep;20(9):1119-21. (PMID: 23934150) ; Protein Sci. 2021 Jan;30(1):70-82. (PMID: 32881101) ; Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13770-4. (PMID: 19666485) ; Sci Adv. 2020 Dec 18;6(51):. (PMID: 33355125) ; Elife. 2018 Aug 06;7:. (PMID: 30079888) ; Nucleic Acids Res. 2017 Aug 21;45(14):8129-8141. (PMID: 28854736) ; J Struct Biol. 2021 Jun;213(2):107702. (PMID: 33582281) ; Mol Cell Biol. 2015 Dec;35(23):4083-92. (PMID: 26416878) ; Elife. 2018 Jun 01;7:. (PMID: 29856314) ; Nature. 2019 Mar;567(7748):409-413. (PMID: 30867599) ; Proc Natl Acad Sci U S A. 2013 May 21;110(21):8495-500. (PMID: 23650358) ; Genes Dev. 2019 Jun 1;33(11-12):620-625. (PMID: 30923167) ; Mol Cell. 2010 Sep 10;39(5):711-23. (PMID: 20832723) ; Bioessays. 2010 May;32(5):422-9. (PMID: 20414900) ; Nat Cell Biol. 2021 Feb;23(2):160-171. (PMID: 33462394) ; Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):861-877. (PMID: 31588918) ; Science. 2021 Jan 22;371(6527):. (PMID: 33479123) ; Nat Struct Mol Biol. 2021 Jan;28(1):71-80. (PMID: 33288924) ; Elife. 2018 Nov 09;7:. (PMID: 30412051) ; J Mol Biol. 2014 May 15;426(10):2034-44. (PMID: 24607692) ; Nucleic Acids Res. 2018 Jul 2;46(W1):W296-W303. (PMID: 29788355) ; Nat Struct Mol Biol. 2008 Oct;15(10):1122-4. (PMID: 18794842) ; Mol Cell. 2017 Mar 2;65(5):932-940.e6. (PMID: 28190768) ; Nat Struct Mol Biol. 2005 Sep;12(9):747-55. (PMID: 16086025) ; Mol Cancer Ther. 2020 Aug;19(8):1598-1612. (PMID: 32499299) ; J Mol Biol. 1998 Feb 13;276(1):19-42. (PMID: 9514715) ; Acta Crystallogr D Struct Biol. 2018 Jun 1;74(Pt 6):519-530. (PMID: 29872003) ; Nat Struct Mol Biol. 2019 Jan;26(1):3-13. (PMID: 30532059) ; Mol Cell Biol. 2011 Dec;31(23):4746-59. (PMID: 21969605) ; Acc Chem Res. 2021 Aug 17;54(16):3215-3227. (PMID: 34319695) ; Nat Methods. 2020 Dec;17(12):1214-1221. (PMID: 33257830) ; Nature. 2019 Sep;573(7774):445-449. (PMID: 31485071) ; Methods Enzymol. 2016;573:3-41. (PMID: 27372747) ; Mol Cell. 2017 Dec 7;68(5):860-871.e7. (PMID: 29220653) ; Nat Struct Mol Biol. 2006 Dec;13(12):1078-83. (PMID: 17099699) ; J Biol Chem. 2004 Sep 17;279(38):39933-41. (PMID: 15262970) ; Cell Rep. 2020 Dec 22;33(12):108529. (PMID: 33357431) ; Cell. 2013 Jan 31;152(3):442-52. (PMID: 23374341) ; Nat Methods. 2017 Apr;14(4):331-332. (PMID: 28250466) ; Nature. 2012 Dec 13;492(7428):280-4. (PMID: 23143334) ; Nature. 2020 Mar;579(7799):448-451. (PMID: 32188943) ; Elife. 2019 Dec 30;8:. (PMID: 31886770) ; Chem Rev. 2015 Mar 25;115(6):2255-73. (PMID: 25495456) ; Mol Cell. 2010 Jul 9;39(1):8-24. (PMID: 20603072) ; Mol Cell. 2019 Jun 6;74(5):1010-1019.e6. (PMID: 30981630) ; Nucleic Acids Res. 2014 Jul;42(12):7762-75. (PMID: 24928857) ; J Mol Biol. 2010 Oct 15;403(1):1-10. (PMID: 20800598) ; Nature. 2018 Apr;556(7701):386-390. (PMID: 29643509) ; Elife. 2017 Mar 23;6:. (PMID: 28332978) ; Protein Sci. 2018 Jan;27(1):14-25. (PMID: 28710774) ; Nature. 2014 Aug 14;512(7513):213-7. (PMID: 25043036) ; Nat Struct Mol Biol. 2020 Jan;27(1):8-13. (PMID: 31819277) ; Elife. 2021 Sep 06;10:. (PMID: 34486521) Grant Information: FC0010048 United Kingdom MRC_ Medical Research Council; R01 GM135599 United States GM NIGMS NIH HHS; FC0010048 United Kingdom CRUK_ Cancer Research UK; 28990 United Kingdom CRUK_ Cancer Research UK; FC0010048 United Kingdom WT_ Wellcome Trust; United Kingdom WT_ Wellcome Trust Contributed Indexing: Keywords: ALC1/CHD1L; PARP1; chromatin; chromosomes; gene expression; human; molecular biophysics; nucleosome; poly(ADP-ribose)ylation; remodeling; structural biology Substance Nomenclature: 0 (Carrier Proteins) ; 0 (DNA-Binding Proteins) ; 0 (HPF1 protein, human) ; 0 (Nuclear Proteins) ; 0 (Nucleosomes) ; 0 (Recombinant Proteins) ; EC 2.4.2.30 (PARP1 protein, human) ; EC 2.4.2.30 (PARP2 protein, human) ; EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1) ; EC 2.4.2.30 (Poly(ADP-ribose) Polymerases) ; EC 3.6.4.- (DNA Helicases) ; EC 3.6.4.12 (CHD1L protein, human) Entry Date(s): Date Created: 20210906 Date Completed: 20211018 Latest Revision: 20240404 Update Code: 20240404 PubMed Central ID: PMC8463071

Klicken Sie ein Format an und speichern Sie dann die Daten oder geben Sie eine Empfänger-Adresse ein und lassen Sie sich per Email zusenden.

BibTeX Citavi, JabRef, u.a.
(Literaturverwaltung)

PDF kein Volltext!
(Merkzettel, Notizen)

RIS Endnote, Citavi u.a.
(Literaturverwaltung)

MODS
(XML zur Weiterverarbeitung)

oder

Wählen Sie das für Sie passende Zitationsformat und kopieren Sie es dann in die Zwischenablage, lassen es sich per Mail zusenden oder speichern es als PDF-Datei.

Gewünschter Zitations-Stil:

oder

Bitte prüfen Sie, ob die Zitation formal korrekt ist, bevor Sie sie in einer Arbeit verwenden. Benutzen Sie gegebenenfalls den "Exportieren"-Dialog, wenn Sie ein Literaturverwaltungsprogramm verwenden und die Zitat-Angaben selbst formatieren wollen.

Structure and dynamics of the chromatin remodeler ALC1 bound to a PARylated nucleosome.