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Optimised oligonucleotide substrates to assay XPF-ERCC1 nuclease activity for the discovery of DNA repair inhibitors.

Thomas AM, Brolih S, McGouran JF, El-Sagheer AH, Ptchelkine D, Jones M, McDonald NQ, McHugh PJ, Brown T.

Chem Commun (Camb). 2019 Sep 9. doi: 10.1039/c9cc05476f. [Epub ahead of print]


RPEL-family rhoGAPs link Rac/Cdc42 GTP loading to G-actin availability.

Diring J, Mouilleron S, McDonald NQ, Treisman R.

Nat Cell Biol. 2019 Jul;21(7):845-855. doi: 10.1038/s41556-019-0337-y. Epub 2019 Jun 17.


Competitive Inhibition of aPKC by Par-3/Bazooka and Other Substrates.

Thompson BJ, McDonald NQ.

Dev Cell. 2019 Jun 3;49(5):680. doi: 10.1016/j.devcel.2019.05.031. No abstract available.


The Rho family GEF FARP2 is activated by aPKCι to control tight junction formation and polarity.

Elbediwy A, Zhang Y, Cobbaut M, Riou P, Tan RS, Roberts SK, Tynan C, George R, Kjaer S, Martin-Fernandez ML, Thompson BJ, McDonald NQ, Parker PJ.

J Cell Sci. 2019 Apr 25;132(8). pii: jcs223743. doi: 10.1242/jcs.223743.


Insights into Current Tropomyosin Receptor Kinase (TRK) Inhibitors: Development and Clinical Application.

Yan W, Lakkaniga NR, Carlomagno F, Santoro M, McDonald NQ, Lv F, Gunaganti N, Frett B, Li HY.

J Med Chem. 2019 Feb 28;62(4):1731-1760. doi: 10.1021/acs.jmedchem.8b01092. Epub 2018 Sep 19.


A secondary RET mutation in the activation loop conferring resistance to vandetanib.

Nakaoku T, Kohno T, Araki M, Niho S, Chauhan R, Knowles PP, Tsuchihara K, Matsumoto S, Shimada Y, Mimaki S, Ishii G, Ichikawa H, Nagatoishi S, Tsumoto K, Okuno Y, Yoh K, McDonald NQ, Goto K.

Nat Commun. 2018 Feb 12;9(1):625. doi: 10.1038/s41467-018-02994-7.


Drugging the catalytically inactive state of RET kinase in RET-rearranged tumors.

Plenker D, Riedel M, Brägelmann J, Dammert MA, Chauhan R, Knowles PP, Lorenz C, Keul M, Bührmann M, Pagel O, Tischler V, Scheel AH, Schütte D, Song Y, Stark J, Mrugalla F, Alber Y, Richters A, Engel J, Leenders F, Heuckmann JM, Wolf J, Diebold J, Pall G, Peifer M, Aerts M, Gevaert K, Zahedi RP, Buettner R, Shokat KM, McDonald NQ, Kast SM, Gautschi O, Thomas RK, Sos ML.

Sci Transl Med. 2017 Jun 14;9(394). pii: eaah6144. doi: 10.1126/scitranslmed.aah6144.


RET Functions as a Dual-Specificity Kinase that Requires Allosteric Inputs from Juxtamembrane Elements.

Plaza-Menacho I, Barnouin K, Barry R, Borg A, Orme M, Chauhan R, Mouilleron S, Martínez-Torres RJ, Meier P, McDonald NQ.

Cell Rep. 2016 Dec 20;17(12):3319-3332. doi: 10.1016/j.celrep.2016.11.061.


aPKC Inhibition by Par3 CR3 Flanking Regions Controls Substrate Access and Underpins Apical-Junctional Polarization.

Soriano EV, Ivanova ME, Fletcher G, Riou P, Knowles PP, Barnouin K, Purkiss A, Kostelecky B, Saiu P, Linch M, Elbediwy A, Kjær S, O'Reilly N, Snijders AP, Parker PJ, Thompson BJ, McDonald NQ.

Dev Cell. 2016 Aug 22;38(4):384-98. doi: 10.1016/j.devcel.2016.07.018.


Exon Skipping in the RET Gene Encodes Novel Isoforms That Differentially Regulate RET Protein Signal Transduction.

Gabreski NA, Vaghasia JK, Novakova SS, McDonald NQ, Pierchala BA.

J Biol Chem. 2016 Jul 29;291(31):16249-62. doi: 10.1074/jbc.M115.709675. Epub 2016 May 23.


The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity.

Newton R, Bowler KA, Burns EM, Chapman PJ, Fairweather EE, Fritzl SJR, Goldberg KM, Hamilton NM, Holt SV, Hopkins GV, Jones SD, Jordan AM, Lyons AJ, Nikki March H, McDonald NQ, Maguire LA, Mould DP, Purkiss AG, Small HF, Stowell AIJ, Thomson GJ, Waddell ID, Waszkowycz B, Watson AJ, Ogilvie DJ.

Eur J Med Chem. 2016 Apr 13;112:20-32. doi: 10.1016/j.ejmech.2016.01.039. Epub 2016 Jan 29.


Structures of the human Pals1 PDZ domain with and without ligand suggest gated access of Crb to the PDZ peptide-binding groove.

Ivanova ME, Fletcher GC, O'Reilly N, Purkiss AG, Thompson BJ, McDonald NQ.

Acta Crystallogr D Biol Crystallogr. 2015 Mar;71(Pt 3):555-64. doi: 10.1107/S139900471402776X. Epub 2015 Feb 26.


RET recognition of GDNF-GFRα1 ligand by a composite binding site promotes membrane-proximal self-association.

Goodman KM, Kjær S, Beuron F, Knowles PP, Nawrotek A, Burns EM, Purkiss AG, George R, Santoro M, Morris EP, McDonald NQ.

Cell Rep. 2014 Sep 25;8(6):1894-1904. doi: 10.1016/j.celrep.2014.08.040. Epub 2014 Sep 18.


Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution.

Fisher R, Horswell S, Rowan A, Salm MP, de Bruin EC, Gulati S, McGranahan N, Stares M, Gerlinger M, Varela I, Crockford A, Favero F, Quidville V, André F, Navas C, Grönroos E, Nicol D, Hazell S, Hrouda D, O'Brien T, Matthews N, Phillimore B, Begum S, Rabinowitz A, Biggs J, Bates PA, McDonald NQ, Stamp G, Spencer-Dene B, Hsieh JJ, Xu J, Pickering L, Gore M, Larkin J, Swanton C.

Genome Biol. 2014 Aug 27;15(8):433. doi: 10.1186/s13059-014-0433-z.


Mechanisms of RET signaling in cancer: current and future implications for targeted therapy.

Plaza-Menacho I, Mologni L, McDonald NQ.

Cell Signal. 2014 Aug;26(8):1743-52. doi: 10.1016/j.cellsig.2014.03.032. Epub 2014 Apr 3. Review.


Oncogenic RET kinase domain mutations perturb the autophosphorylation trajectory by enhancing substrate presentation in trans.

Plaza-Menacho I, Barnouin K, Goodman K, Martínez-Torres RJ, Borg A, Murray-Rust J, Mouilleron S, Knowles P, McDonald NQ.

Mol Cell. 2014 Mar 6;53(5):738-51. doi: 10.1016/j.molcel.2014.01.015. Epub 2014 Feb 20.


Functional implications of assigned, assumed and assembled PKC structures.

Linch M, Riou P, Claus J, Cameron AJ, de Naurois J, Larijani B, Ng T, McDonald NQ, Parker PJ.

Biochem Soc Trans. 2014 Feb;42(1):35-41. doi: 10.1042/BST20130192.


A cancer-associated mutation in atypical protein kinase Cι occurs in a substrate-specific recruitment motif.

Linch M, Sanz-Garcia M, Soriano E, Zhang Y, Riou P, Rosse C, Cameron A, Knowles P, Purkiss A, Kjaer S, McDonald NQ, Parker PJ.

Sci Signal. 2013 Sep 17;6(293):ra82. doi: 10.1126/scisignal.2004068.


A winged helix domain in human MUS81 binds DNA and modulates the endonuclease activity of MUS81 complexes.

Fadden AJ, Schalbetter S, Bowles M, Harris R, Lally J, Carr AM, McDonald NQ.

Nucleic Acids Res. 2013 Nov;41(21):9741-52. doi: 10.1093/nar/gkt760. Epub 2013 Aug 27.


Architecture and DNA recognition elements of the Fanconi anemia FANCM-FAAP24 complex.

Coulthard R, Deans AJ, Swuec P, Bowles M, Costa A, West SC, McDonald NQ.

Structure. 2013 Sep 3;21(9):1648-58. doi: 10.1016/j.str.2013.07.006. Epub 2013 Aug 8.


14-3-3 proteins interact with a hybrid prenyl-phosphorylation motif to inhibit G proteins.

Riou P, Kjær S, Garg R, Purkiss A, George R, Cain RJ, Bineva G, Reymond N, McColl B, Thompson AJ, O'Reilly N, McDonald NQ, Parker PJ, Ridley AJ.

Cell. 2013 Apr 25;153(3):640-53. doi: 10.1016/j.cell.2013.03.044. Erratum in: Cell. 2013 May 23;153(5):1164.


Adenosine-binding motif mimicry and cellular effects of a thieno[2,3-d]pyrimidine-based chemical inhibitor of atypical protein kinase C isoenzymes.

Kjær S, Linch M, Purkiss A, Kostelecky B, Knowles PP, Rosse C, Riou P, Soudy C, Kaye S, Patel B, Soriano E, Murray-Rust J, Barton C, Dillon C, Roffey J, Parker PJ, McDonald NQ.

Biochem J. 2013 Apr 15;451(2):329-42. doi: 10.1042/BJ20121871.


Structures of the Phactr1 RPEL domain and RPEL motif complexes with G-actin reveal the molecular basis for actin binding cooperativity.

Mouilleron S, Wiezlak M, O'Reilly N, Treisman R, McDonald NQ.

Structure. 2012 Nov 7;20(11):1960-70. doi: 10.1016/j.str.2012.08.031. Epub 2012 Oct 4.


G-actin regulates the shuttling and PP1 binding of the RPEL protein Phactr1 to control actomyosin assembly.

Wiezlak M, Diring J, Abella J, Mouilleron S, Way M, McDonald NQ, Treisman R.

J Cell Sci. 2012 Dec 1;125(Pt 23):5860-72. doi: 10.1242/jcs.112078. Epub 2012 Sep 12.


Fluorescence-based incision assay for human XPF-ERCC1 activity identifies important elements of DNA junction recognition.

Bowles M, Lally J, Fadden AJ, Mouilleron S, Hammonds T, McDonald NQ.

Nucleic Acids Res. 2012 Jul;40(13):e101. doi: 10.1093/nar/gks284. Epub 2012 Mar 28.


Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.

Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C.

N Engl J Med. 2012 Mar 8;366(10):883-892. doi: 10.1056/NEJMoa1113205. Erratum in: N Engl J Med. 2012 Sep 6;367(10):976.


Structure of a pentavalent G-actin*MRTF-A complex reveals how G-actin controls nucleocytoplasmic shuttling of a transcriptional coactivator.

Mouilleron S, Langer CA, Guettler S, McDonald NQ, Treisman R.

Sci Signal. 2011 Jun 14;4(177):ra40. doi: 10.1126/scisignal.2001750.


Focal adhesion kinase (FAK) binds RET kinase via its FERM domain, priming a direct and reciprocal RET-FAK transactivation mechanism.

Plaza-Menacho I, Morandi A, Mologni L, Boender P, Gambacorti-Passerini C, Magee AI, Hofstra RM, Knowles P, McDonald NQ, Isacke CM.

J Biol Chem. 2011 May 13;286(19):17292-302. doi: 10.1074/jbc.M110.168500. Epub 2011 Mar 22.


Molecular recognition of the Tes LIM2-3 domains by the actin-related protein Arp7A.

Boëda B, Knowles PP, Briggs DC, Murray-Rust J, Soriano E, Garvalov BK, McDonald NQ, Way M.

J Biol Chem. 2011 Apr 1;286(13):11543-54. doi: 10.1074/jbc.M110.171264. Epub 2011 Jan 29.


Mammal-restricted elements predispose human RET to folding impairment by HSCR mutations.

Kjaer S, Hanrahan S, Totty N, McDonald NQ.

Nat Struct Mol Biol. 2010 Jun;17(6):726-31. doi: 10.1038/nsmb.1808. Epub 2010 May 16.


Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors.

Mologni L, Rostagno R, Brussolo S, Knowles PP, Kjaer S, Murray-Rust J, Rosso E, Zambon A, Scapozza L, McDonald NQ, Lucchini V, Gambacorti-Passerini C.

Bioorg Med Chem. 2010 Feb 15;18(4):1482-96. doi: 10.1016/j.bmc.2010.01.011. Epub 2010 Jan 11.


Recognition of an intra-chain tandem 14-3-3 binding site within PKCepsilon.

Kostelecky B, Saurin AT, Purkiss A, Parker PJ, McDonald NQ.

EMBO Rep. 2009 Sep;10(9):983-9. doi: 10.1038/embor.2009.150. Epub 2009 Aug 7.


Protein kinase C intervention: the state of play.

Roffey J, Rosse C, Linch M, Hibbert A, McDonald NQ, Parker PJ.

Curr Opin Cell Biol. 2009 Apr;21(2):268-79. doi: 10.1016/ Epub 2009 Feb 23. Review.


Identification of tyrosine 806 as a molecular determinant of RET kinase sensitivity to ZD6474.

Carlomagno F, Guida T, Anaganti S, Provitera L, Kjaer S, McDonald NQ, Ryan AJ, Santoro M.

Endocr Relat Cancer. 2009 Mar;16(1):233-41. doi: 10.1677/ERC-08-0213. Epub 2008 Nov 24.


Molecular basis for G-actin binding to RPEL motifs from the serum response factor coactivator MAL.

Mouilleron S, Guettler S, Langer CA, Treisman R, McDonald NQ.

EMBO J. 2008 Dec 3;27(23):3198-208. doi: 10.1038/emboj.2008.235. Epub 2008 Nov 13.


Structure of a conserved dimerization domain within the F-box protein Fbxo7 and the PI31 proteasome inhibitor.

Kirk R, Laman H, Knowles PP, Murray-Rust J, Lomonosov M, Meziane el K, McDonald NQ.

J Biol Chem. 2008 Aug 8;283(32):22325-35. doi: 10.1074/jbc.M709900200. Epub 2008 May 20.


Crystallization and preliminary X-ray diffraction analysis of vaccinia virus H1L phosphatase.

Roces L, Knowles PP, Fox G, Juanhuix J, Scaplehorn N, Way M, McDonald NQ.

Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Mar 1;64(Pt 3):190-2. doi: 10.1107/S1744309108003680. Epub 2008 Feb 23.


Tes, a specific Mena interacting partner, breaks the rules for EVH1 binding.

Boëda B, Briggs DC, Higgins T, Garvalov BK, Fadden AJ, McDonald NQ, Way M.

Mol Cell. 2007 Dec 28;28(6):1071-82.


Redox-mediated substrate recognition by Sdp1 defines a new group of tyrosine phosphatases.

Fox GC, Shafiq M, Briggs DC, Knowles PP, Collister M, Didmon MJ, Makrantoni V, Dickinson RJ, Hanrahan S, Totty N, Stark MJ, Keyse SM, McDonald NQ.

Nature. 2007 May 24;447(7143):487-92. Epub 2007 May 9.


Disruption of methylarginine metabolism impairs vascular homeostasis.

Leiper J, Nandi M, Torondel B, Murray-Rust J, Malaki M, O'Hara B, Rossiter S, Anthony S, Madhani M, Selwood D, Smith C, Wojciak-Stothard B, Rudiger A, Stidwill R, McDonald NQ, Vallance P.

Nat Med. 2007 Feb;13(2):198-203. Epub 2007 Feb 4.


A small molecule inhibitor for phosphatase and tensin homologue deleted on chromosome 10 (PTEN).

Rosivatz E, Matthews JG, McDonald NQ, Mulet X, Ho KK, Lossi N, Schmid AC, Mirabelli M, Pomeranz KM, Erneux C, Lam EW, Vilar R, Woscholski R.

ACS Chem Biol. 2006 Dec 15;1(12):780-90.


A heterozygous effect for PINK1 mutations in Parkinson's disease?

Abou-Sleiman PM, Muqit MM, McDonald NQ, Yang YX, Gandhi S, Healy DG, Harvey K, Harvey RJ, Deas E, Bhatia K, Quinn N, Lees A, Latchman DS, Wood NW.

Ann Neurol. 2006 Oct;60(4):414-9.


Structure and chemical inhibition of the RET tyrosine kinase domain.

Knowles PP, Murray-Rust J, Kjaer S, Scott RP, Hanrahan S, Santoro M, Ibáñez CF, McDonald NQ.

J Biol Chem. 2006 Nov 3;281(44):33577-87. Epub 2006 Aug 23.


The solution structure of the Josephin domain of ataxin-3: structural determinants for molecular recognition.

Nicastro G, Menon RP, Masino L, Knowles PP, McDonald NQ, Pastore A.

Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10493-8. Epub 2005 Jul 14.


Structure of an XPF endonuclease with and without DNA suggests a model for substrate recognition.

Newman M, Murray-Rust J, Lally J, Rudolf J, Fadden A, Knowles PP, White MF, McDonald NQ.

EMBO J. 2005 Mar 9;24(5):895-905. Epub 2005 Feb 17.


Structure-function analysis of human [corrected] phosphatidylinositol transfer protein alpha bound to phosphatidylinositol.

Tilley SJ, Skippen A, Murray-Rust J, Swigart PM, Stewart A, Morgan CP, Cockcroft S, McDonald NQ.

Structure. 2004 Feb;12(2):317-26. Erratum in: Structure (Camb). 2004 May;12(5):907.


The Mycobacterium tuberculosis ino1 gene is essential for growth and virulence.

Movahedzadeh F, Smith DA, Norman RA, Dinadayala P, Murray-Rust J, Russell DG, Kendall SL, Rison SC, McAlister MS, Bancroft GJ, McDonald NQ, Daffe M, Av-Gay Y, Stoker NG.

Mol Microbiol. 2004 Feb;51(4):1003-14.


The dual mechanism of separase regulation by securin.

Hornig NC, Knowles PP, McDonald NQ, Uhlmann F.

Curr Biol. 2002 Jun 25;12(12):973-82.


Crystal structure of inositol 1-phosphate synthase from Mycobacterium tuberculosis, a key enzyme in phosphatidylinositol synthesis.

Norman RA, McAlister MS, Murray-Rust J, Movahedzadeh F, Stoker NG, McDonald NQ.

Structure. 2002 Mar;10(3):393-402.


Structure-activity relationship of the p55 TNF receptor death domain and its lymphoproliferation mutants.

De Wilde G, Murray-Rust J, Boone E, Olerenshaw D, McDonald NQ, Ibanez C, Haegeman G, Wollmer A, Federwisch M.

Eur J Biochem. 2001 Mar;268(5):1382-91.

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