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The unstructured linker arms of MutL enable GATC site incision beyond roadblocks during initiation of DNA mismatch repair.

Mardenborough YSN, Nitsenko K, Laffeber C, Duboc C, Sahin E, Quessada-Vial A, Winterwerp HHK, Sixma TK, Kanaar R, Friedhoff P, Strick TR, Lebbink JHG.

Nucleic Acids Res. 2019 Dec 16;47(22):11667-11680. doi: 10.1093/nar/gkz834.


Sharp kinking of a coiled-coil in MutS allows DNA binding and release.

Bhairosing-Kok D, Groothuizen FS, Fish A, Dharadhar S, Winterwerp HHK, Sixma TK.

Nucleic Acids Res. 2019 Sep 19;47(16):8888-8898. doi: 10.1093/nar/gkz649.


Structural basis of specific H2A K13/K15 ubiquitination by RNF168.

Horn V, Uckelmann M, Zhang H, Eerland J, Aarsman I, le Paige UB, Davidovich C, Sixma TK, van Ingen H.

Nat Commun. 2019 Apr 15;10(1):1751. doi: 10.1038/s41467-019-09756-z.


Quantitative analysis of USP activity in vitro.

Dharadhar S, Kim RQ, Uckelmann M, Sixma TK.

Methods Enzymol. 2019;618:281-319. doi: 10.1016/bs.mie.2018.12.023. Epub 2019 Feb 23.


Kinetic analysis of multistep USP7 mechanism shows critical role for target protein in activity.

Kim RQ, Geurink PP, Mulder MPC, Fish A, Ekkebus R, El Oualid F, van Dijk WJ, van Dalen D, Ovaa H, van Ingen H, Sixma TK.

Nat Commun. 2019 Jan 16;10(1):231. doi: 10.1038/s41467-018-08231-5.


Active site alanine mutations convert deubiquitinases into high-affinity ubiquitin-binding proteins.

Morrow ME, Morgan MT, Clerici M, Growkova K, Yan M, Komander D, Sixma TK, Simicek M, Wolberger C.

EMBO Rep. 2018 Oct;19(10). pii: e45680. doi: 10.15252/embr.201745680. Epub 2018 Aug 27.


ZUFSP Deubiquitylates K63-Linked Polyubiquitin Chains to Promote Genome Stability.

Haahr P, Borgermann N, Guo X, Typas D, Achuthankutty D, Hoffmann S, Shearer R, Sixma TK, Mailand N.

Mol Cell. 2018 Apr 5;70(1):165-174.e6. doi: 10.1016/j.molcel.2018.02.024. Epub 2018 Mar 22.


USP48 restrains resection by site-specific cleavage of the BRCA1 ubiquitin mark from H2A.

Uckelmann M, Densham RM, Baas R, Winterwerp HHK, Fish A, Sixma TK, Morris JR.

Nat Commun. 2018 Jan 15;9(1):229. doi: 10.1038/s41467-017-02653-3.


Use of Single-Cysteine Variants for Trapping Transient States in DNA Mismatch Repair.

Friedhoff P, Manelyte L, Giron-Monzon L, Winkler I, Groothuizen FS, Sixma TK.

Methods Enzymol. 2017;592:77-101. doi: 10.1016/bs.mie.2017.03.025. Epub 2017 May 22.


Histone ubiquitination in the DNA damage response.

Uckelmann M, Sixma TK.

DNA Repair (Amst). 2017 Aug;56:92-101. doi: 10.1016/j.dnarep.2017.06.011. Epub 2017 Jun 9. Review.


Regulation of USP7: A High Incidence of E3 Complexes.

Kim RQ, Sixma TK.

J Mol Biol. 2017 Nov 10;429(22):3395-3408. doi: 10.1016/j.jmb.2017.05.028. Epub 2017 Jun 4. Review.


USP4 inhibits SMAD4 monoubiquitination and promotes activin and BMP signaling.

Zhou F, Xie F, Jin K, Zhang Z, Clerici M, Gao R, van Dinther M, Sixma TK, Huang H, Zhang L, Ten Dijke P.

EMBO J. 2017 Jun 1;36(11):1623-1639. doi: 10.15252/embj.201695372. Epub 2017 May 3.


A conserved two-step binding for the UAF1 regulator to the USP12 deubiquitinating enzyme.

Dharadhar S, Clerici M, van Dijk WJ, Fish A, Sixma TK.

J Struct Biol. 2016 Dec;196(3):437-447. doi: 10.1016/j.jsb.2016.09.011. Epub 2016 Sep 17.


Structure of USP7 catalytic domain and three Ubl-domains reveals a connector α-helix with regulatory role.

Kim RQ, van Dijk WJ, Sixma TK.

J Struct Biol. 2016 Jul;195(1):11-8. doi: 10.1016/j.jsb.2016.05.005. Epub 2016 May 13.


LNA modification of single-stranded DNA oligonucleotides allows subtle gene modification in mismatch-repair-proficient cells.

van Ravesteyn TW, Dekker M, Fish A, Sixma TK, Wolters A, Dekker RJ, Te Riele HP.

Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):4122-7. doi: 10.1073/pnas.1513315113. Epub 2016 Mar 7.


The conserved molecular machinery in DNA mismatch repair enzyme structures.

Groothuizen FS, Sixma TK.

DNA Repair (Amst). 2016 Feb;38:14-23. doi: 10.1016/j.dnarep.2015.11.012. Epub 2015 Dec 2. Review.


Touch, act and go: landing and operating on nucleosomes.

Speranzini V, Pilotto S, Sixma TK, Mattevi A.

EMBO J. 2016 Feb 15;35(4):376-88. doi: 10.15252/embj.201593377. Epub 2016 Jan 19. Review.


BAP1/ASXL1 recruitment and activation for H2A deubiquitination.

Sahtoe DD, van Dijk WJ, Ekkebus R, Ovaa H, Sixma TK.

Nat Commun. 2016 Jan 7;7:10292. doi: 10.1038/ncomms10292.


Structure of UBE2Z Enzyme Provides Functional Insight into Specificity in the FAT10 Protein Conjugation Machinery.

Schelpe J, Monté D, Dewitte F, Sixma TK, Rucktooa P.

J Biol Chem. 2016 Jan 8;291(2):630-9. doi: 10.1074/jbc.M115.671545. Epub 2015 Nov 10.


Histone H1 couples initiation and amplification of ubiquitin signalling after DNA damage.

Thorslund T, Ripplinger A, Hoffmann S, Wild T, Uckelmann M, Villumsen B, Narita T, Sixma TK, Choudhary C, Bekker-Jensen S, Mailand N.

Nature. 2015 Nov 19;527(7578):389-93. doi: 10.1038/nature15401. Epub 2015 Oct 21.


MutS/MutL crystal structure reveals that the MutS sliding clamp loads MutL onto DNA.

Groothuizen FS, Winkler I, Cristóvão M, Fish A, Winterwerp HH, Reumer A, Marx AD, Hermans N, Nicholls RA, Murshudov GN, Lebbink JH, Friedhoff P, Sixma TK.

Elife. 2015 Jul 11;4:e06744. doi: 10.7554/eLife.06744.


Layers of DUB regulation.

Sahtoe DD, Sixma TK.

Trends Biochem Sci. 2015 Aug;40(8):456-67. doi: 10.1016/j.tibs.2015.05.002. Epub 2015 Jun 11. Review.


Make them, break them, and catch them: studying rare ubiquitin chains.

Uckelmann M, Sixma TK.

Mol Cell. 2015 Apr 2;58(1):1-2. doi: 10.1016/j.molcel.2015.03.024.


Interplay among nucleosomal DNA, histone tails, and corepressor CoREST underlies LSD1-mediated H3 demethylation.

Pilotto S, Speranzini V, Tortorici M, Durand D, Fish A, Valente S, Forneris F, Mai A, Sixma TK, Vachette P, Mattevi A.

Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):2752-7. doi: 10.1073/pnas.1419468112. Epub 2015 Feb 17.


Mechanism of UCH-L5 activation and inhibition by DEUBAD domains in RPN13 and INO80G.

Sahtoe DD, van Dijk WJ, El Oualid F, Ekkebus R, Ovaa H, Sixma TK.

Mol Cell. 2015 Mar 5;57(5):887-900. doi: 10.1016/j.molcel.2014.12.039. Epub 2015 Feb 19.


The DUSP-Ubl domain of USP4 enhances its catalytic efficiency by promoting ubiquitin exchange.

Clerici M, Luna-Vargas MP, Faesen AC, Sixma TK.

Nat Commun. 2014 Nov 18;5:5399. doi: 10.1038/ncomms6399.


Lysine-targeting specificity in ubiquitin and ubiquitin-like modification pathways.

Mattiroli F, Sixma TK.

Nat Struct Mol Biol. 2014 Apr;21(4):308-16. doi: 10.1038/nsmb.2792. Review.


The nucleosome acidic patch plays a critical role in RNF168-dependent ubiquitination of histone H2A.

Mattiroli F, Uckelmann M, Sahtoe DD, van Dijk WJ, Sixma TK.

Nat Commun. 2014;5:3291. doi: 10.1038/ncomms4291. Erratum in: Nat Commun. 2014;5:3692.


RBR E3-ligases at work.

Smit JJ, Sixma TK.

EMBO Rep. 2014 Feb;15(2):142-54. doi: 10.1002/embr.201338166. Epub 2014 Jan 27. Review.


The seven wonders of ubiquitin: a multi-interview: Personal insights into the ubiquitin field. Interview by Nonia Pariente.

Dikic I, Harper W, Hay R, Langer T, Rape M, Sixma T, Walczak H.

EMBO Rep. 2014 Jan;15(1):7-11. doi: 10.1002/embr.201338230. No abstract available.


Target specificity of the E3 ligase LUBAC for ubiquitin and NEMO relies on different minimal requirements.

Smit JJ, van Dijk WJ, El Atmioui D, Merkx R, Ovaa H, Sixma TK.

J Biol Chem. 2013 Nov 1;288(44):31728-37. doi: 10.1074/jbc.M113.495846. Epub 2013 Sep 12.


Using stable MutS dimers and tetramers to quantitatively analyze DNA mismatch recognition and sliding clamp formation.

Groothuizen FS, Fish A, Petoukhov MV, Reumer A, Manelyte L, Winterwerp HH, Marinus MG, Lebbink JH, Svergun DI, Friedhoff P, Sixma TK.

Nucleic Acids Res. 2013 Sep;41(17):8166-81. doi: 10.1093/nar/gkt582. Epub 2013 Jul 1.


Assembly of a π-π stack of ligands in the binding site of an acetylcholine-binding protein.

Stornaiuolo M, De Kloe GE, Rucktooa P, Fish A, van Elk R, Edink ES, Bertrand D, Smit AB, de Esch IJ, Sixma TK.

Nat Commun. 2013;4:1875. doi: 10.1038/ncomms2900.


Protein engineering: making ubiquitin specific.

Sixma TK.

Nat Chem Biol. 2013 Jan;9(1):10-1. doi: 10.1038/nchembio.1143. No abstract available.


Intrinsic flexibility of ubiquitin on proliferating cell nuclear antigen (PCNA) in translesion synthesis.

Hibbert RG, Sixma TK.

J Biol Chem. 2012 Nov 9;287(46):39216-23. doi: 10.1074/jbc.M112.389890. Epub 2012 Sep 18.


RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling.

Mattiroli F, Vissers JH, van Dijk WJ, Ikpa P, Citterio E, Vermeulen W, Marteijn JA, Sixma TK.

Cell. 2012 Sep 14;150(6):1182-95. doi: 10.1016/j.cell.2012.08.005.


The E3 ligase HOIP specifies linear ubiquitin chain assembly through its RING-IBR-RING domain and the unique LDD extension.

Smit JJ, Monteferrario D, Noordermeer SM, van Dijk WJ, van der Reijden BA, Sixma TK.

EMBO J. 2012 Oct 3;31(19):3833-44. doi: 10.1038/emboj.2012.217. Epub 2012 Aug 3.


A deubiquitylating complex required for neosynthesis of a yeast mitochondrial ATP synthase subunit.

Kanga S, Bernard D, Mager-Heckel AM, Erpapazoglou Z, Mattiroli F, Sixma TK, Léon S, Urban-Grimal D, Tarassov I, Haguenauer-Tsapis R.

PLoS One. 2012;7(6):e38071. doi: 10.1371/journal.pone.0038071. Epub 2012 Jun 19.


The role of UBL domains in ubiquitin-specific proteases.

Faesen AC, Luna-Vargas MP, Sixma TK.

Biochem Soc Trans. 2012 Jun 1;40(3):539-45. doi: 10.1042/BST20120004. Review.


Transient transfection coupled to baculovirus infection for rapid protein expression screening in insect cells.

Radner S, Celie PH, Fuchs K, Sieghart W, Sixma TK, Stornaiuolo M.

J Struct Biol. 2012 Jul;179(1):46-55. doi: 10.1016/j.jsb.2012.04.013. Epub 2012 May 2.


Structural characterization of binding mode of smoking cessation drugs to nicotinic acetylcholine receptors through study of ligand complexes with acetylcholine-binding protein.

Rucktooa P, Haseler CA, van Elk R, Smit AB, Gallagher T, Sixma TK.

J Biol Chem. 2012 Jul 6;287(28):23283-93. doi: 10.1074/jbc.M112.360347. Epub 2012 May 2.


Akt-mediated phosphorylation of Bmi1 modulates its oncogenic potential, E3 ligase activity, and DNA damage repair activity in mouse prostate cancer.

Nacerddine K, Beaudry JB, Ginjala V, Westerman B, Mattiroli F, Song JY, van der Poel H, Ponz OB, Pritchard C, Cornelissen-Steijger P, Zevenhoven J, Tanger E, Sixma TK, Ganesan S, van Lohuizen M.

J Clin Invest. 2012 May;122(5):1920-32. doi: 10.1172/JCI57477. Epub 2012 Apr 16.


RNF8- and RNF168-dependent degradation of KDM4A/JMJD2A triggers 53BP1 recruitment to DNA damage sites.

Mallette FA, Mattiroli F, Cui G, Young LC, Hendzel MJ, Mer G, Sixma TK, Richard S.

EMBO J. 2012 Apr 18;31(8):1865-78. doi: 10.1038/emboj.2012.47. Epub 2012 Feb 28.


Dimeric α-cobratoxin X-ray structure: localization of intermolecular disulfides and possible mode of binding to nicotinic acetylcholine receptors.

Osipov AV, Rucktooa P, Kasheverov IE, Filkin SY, Starkov VG, Andreeva TV, Sixma TK, Bertrand D, Utkin YN, Tsetlin VI.

J Biol Chem. 2012 Feb 24;287(9):6725-34. doi: 10.1074/jbc.M111.322313. Epub 2012 Jan 5.


The differential modulation of USP activity by internal regulatory domains, interactors and eight ubiquitin chain types.

Faesen AC, Luna-Vargas MP, Geurink PP, Clerici M, Merkx R, van Dijk WJ, Hameed DS, El Oualid F, Ovaa H, Sixma TK.

Chem Biol. 2011 Dec 23;18(12):1550-61. doi: 10.1016/j.chembiol.2011.10.017.


Mechanism of USP7/HAUSP activation by its C-terminal ubiquitin-like domain and allosteric regulation by GMP-synthetase.

Faesen AC, Dirac AM, Shanmugham A, Ovaa H, Perrakis A, Sixma TK.

Mol Cell. 2011 Oct 7;44(1):147-59. doi: 10.1016/j.molcel.2011.06.034.


Acetylcholine binding protein (AChBP) as template for hierarchical in silico screening procedures to identify structurally novel ligands for the nicotinic receptors.

Akdemir A, Rucktooa P, Jongejan A, Elk Rv, Bertrand S, Sixma TK, Bertrand D, Smit AB, Leurs R, de Graaf C, de Esch IJ.

Bioorg Med Chem. 2011 Oct 15;19(20):6107-19. doi: 10.1016/j.bmc.2011.08.028. Epub 2011 Aug 27.


Human RAD18 interacts with ubiquitylated chromatin components and facilitates RAD9 recruitment to DNA double strand breaks.

Inagaki A, Sleddens-Linkels E, van Cappellen WA, Hibbert RG, Sixma TK, Hoeijmakers JH, Grootegoed JA, Baarends WM.

PLoS One. 2011;6(8):e23155. doi: 10.1371/journal.pone.0023155. Epub 2011 Aug 17.


Native mass spectrometry provides direct evidence for DNA mismatch-induced regulation of asymmetric nucleotide binding in mismatch repair protein MutS.

Monti MC, Cohen SX, Fish A, Winterwerp HH, Barendregt A, Friedhoff P, Perrakis A, Heck AJ, Sixma TK, van den Heuvel RH, Lebbink JH.

Nucleic Acids Res. 2011 Oct;39(18):8052-64. doi: 10.1093/nar/gkr498. Epub 2011 Jul 6.


Symmetry and asymmetry of the RING-RING dimer of Rad18.

Huang A, Hibbert RG, de Jong RN, Das D, Sixma TK, Boelens R.

J Mol Biol. 2011 Jul 15;410(3):424-35. doi: 10.1016/j.jmb.2011.04.051. Epub 2011 Apr 27.


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