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Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1 to control the G1 DNA damage checkpoint.

Bigot N, Day M, Baldock RA, Watts FZ, Oliver AW, Pearl LH.

Elife. 2019 May 28;8. pii: e44353. doi: 10.7554/eLife.44353.


Structural mechanism for regulation of the AAA-ATPases RUVBL1-RUVBL2 in the R2TP co-chaperone revealed by cryo-EM.

Muñoz-Hernández H, Pal M, Rodríguez CF, Fernandez-Leiro R, Prodromou C, Pearl LH, Llorca O.

Sci Adv. 2019 May 1;5(5):eaaw1616. doi: 10.1126/sciadv.aaw1616. eCollection 2019 May.


MDC1 Interacts with TOPBP1 to Maintain Chromosomal Stability during Mitosis.

Leimbacher PA, Jones SE, Shorrocks AK, de Marco Zompit M, Day M, Blaauwendraad J, Bundschuh D, Bonham S, Fischer R, Fink D, Kessler BM, Oliver AW, Pearl LH, Blackford AN, Stucki M.

Mol Cell. 2019 May 2;74(3):571-583.e8. doi: 10.1016/j.molcel.2019.02.014. Epub 2019 Mar 18.


Efficient Single-Strand Break Repair Requires Binding to Both Poly(ADP-Ribose) and DNA by the Central BRCT Domain of XRCC1.

Polo LM, Xu Y, Hornyak P, Garces F, Zeng Z, Hailstone R, Matthews SJ, Caldecott KW, Oliver AW, Pearl LH.

Cell Rep. 2019 Jan 15;26(3):573-581.e5. doi: 10.1016/j.celrep.2018.12.082.


Correction: In vitro Biological Characterization of a Novel, Synthetic Diaryl Pyrazole Resorcinol Class of Heat Shock Protein 90 Inhibitors.

Sharp SY, Boxall K, Rowlands M, Prodromou C, Roe SM, Maloney A, Powers M, Clarke PA, Box G, Sanderson S, Patterson L, Matthews TP, Cheung KJ, Ball K, Hayes A, Raynaud F, Marais R, Pearl L, Eccles S, Aherne W, McDonald E, Workman P.

Cancer Res. 2019 Jan 1;79(1):287. doi: 10.1158/0008-5472.CAN-18-3578. No abstract available.


Advances on the Structure of the R2TP/Prefoldin-like Complex.

Muñoz-Hernández H, Pal M, Rodríguez CF, Prodromou C, Pearl LH, Llorca O.

Adv Exp Med Biol. 2018;1106:73-83. doi: 10.1007/978-3-030-00737-9_5.


BRCT domains of the DNA damage checkpoint proteins TOPBP1/Rad4 display distinct specificities for phosphopeptide ligands.

Day M, Rappas M, Ptasinska K, Boos D, Oliver AW, Pearl LH.

Elife. 2018 Oct 8;7. pii: e39979. doi: 10.7554/eLife.39979.


Author Correction: RPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co-chaperone complex.

Martino F, Pal M, Muñoz-Hernández H, Rodríguez CF, Núñez-Ramírez R, Gil-Carton D, Degliesposti G, Skehel JM, Roe SM, Prodromou C, Pearl LH, Llorca O.

Nat Commun. 2018 Jul 31;9(1):3063. doi: 10.1038/s41467-018-05546-1.


RPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co-chaperone complex.

Martino F, Pal M, Muñoz-Hernández H, Rodríguez CF, Núñez-Ramírez R, Gil-Carton D, Degliesposti G, Skehel JM, Roe SM, Prodromou C, Pearl LH, Llorca O.

Nat Commun. 2018 Apr 16;9(1):1501. doi: 10.1038/s41467-018-03942-1. Erratum in: Nat Commun. 2018 Jul 31;9(1):3063.


Differential Regulation of G1 CDK Complexes by the Hsp90-Cdc37 Chaperone System.

Hallett ST, Pastok MW, Morgan RML, Wittner A, Blundell KLIM, Felletar I, Wedge SR, Prodromou C, Noble MEM, Pearl LH, Endicott JA.

Cell Rep. 2017 Oct 31;21(5):1386-1398. doi: 10.1016/j.celrep.2017.10.042.


Structural basis for recruitment of BRCA2 by PALB2.

Oliver AW, Swift S, Lord CJ, Ashworth A, Pearl LH.

EMBO Rep. 2017 Jul;18(7):1264. doi: 10.15252/embr.201744508. No abstract available.


The Structure of the R2TP Complex Defines a Platform for Recruiting Diverse Client Proteins to the HSP90 Molecular Chaperone System.

Rivera-Calzada A, Pal M, Muñoz-Hernández H, Luque-Ortega JR, Gil-Carton D, Degliesposti G, Skehel JM, Prodromou C, Pearl LH, Llorca O.

Structure. 2017 Jul 5;25(7):1145-1152.e4. doi: 10.1016/j.str.2017.05.016. Epub 2017 Jun 22.


HECTD3 Mediates an HSP90-Dependent Degradation Pathway for Protein Kinase Clients.

Li Z, Zhou L, Prodromou C, Savic V, Pearl LH.

Cell Rep. 2017 Jun 20;19(12):2515-2528. doi: 10.1016/j.celrep.2017.05.078.


Motorboat noise impacts parental behaviour and offspring survival in a reef fish.

Nedelec SL, Radford AN, Pearl L, Nedelec B, McCormick MI, Meekan MG, Simpson SD.

Proc Biol Sci. 2017 Jun 14;284(1856). pii: 20170143. doi: 10.1098/rspb.2017.0143.


The structure of FKBP38 in complex with the MEEVD tetratricopeptide binding-motif of Hsp90.

Blundell KL, Pal M, Roe SM, Pearl LH, Prodromou C.

PLoS One. 2017 Mar 9;12(3):e0173543. doi: 10.1371/journal.pone.0173543. eCollection 2017.


Specialized interfaces of Smc5/6 control hinge stability and DNA association.

Alt A, Dang HQ, Wells OS, Polo LM, Smith MA, McGregor GA, Welte T, Lehmann AR, Pearl LH, Murray JM, Oliver AW.

Nat Commun. 2017 Jan 30;8:14011. doi: 10.1038/ncomms14011.


A first generation inhibitor of human Greatwall kinase, enabled by structural and functional characterisation of a minimal kinase domain construct.

Ocasio CA, Rajasekaran MB, Walker S, Le Grand D, Spencer J, Pearl FM, Ward SE, Savic V, Pearl LH, Hochegger H, Oliver AW.

Oncotarget. 2016 Nov 1;7(44):71182-71197. doi: 10.18632/oncotarget.11511.


PARP3 is a sensor of nicked nucleosomes and monoribosylates histone H2B(Glu2).

Grundy GJ, Polo LM, Zeng Z, Rulten SL, Hoch NC, Paomephan P, Xu Y, Sweet SM, Thorne AW, Oliver AW, Matthews SJ, Pearl LH, Caldecott KW.

Nat Commun. 2016 Aug 17;7:12404. doi: 10.1038/ncomms12404.


Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease.

van der Crabben SN, Hennus MP, McGregor GA, Ritter DI, Nagamani SC, Wells OS, Harakalova M, Chinn IK, Alt A, Vondrova L, Hochstenbach R, van Montfrans JM, Terheggen-Lagro SW, van Lieshout S, van Roosmalen MJ, Renkens I, Duran K, Nijman IJ, Kloosterman WP, Hennekam E, Orange JS, van Hasselt PM, Wheeler DA, Palecek JJ, Lehmann AR, Oliver AW, Pearl LH, Plon SE, Murray JM, van Haaften G.

J Clin Invest. 2016 Aug 1;126(8):2881-92. doi: 10.1172/JCI82890. Epub 2016 Jul 18.


Cooperation of local motions in the Hsp90 molecular chaperone ATPase mechanism.

Schulze A, Beliu G, Helmerich DA, Schubert J, Pearl LH, Prodromou C, Neuweiler H.

Nat Chem Biol. 2016 Aug;12(8):628-35. doi: 10.1038/nchembio.2111. Epub 2016 Jun 20.


Human BRCA1-BARD1 ubiquitin ligase activity counteracts chromatin barriers to DNA resection.

Densham RM, Garvin AJ, Stone HR, Strachan J, Baldock RA, Daza-Martin M, Fletcher A, Blair-Reid S, Beesley J, Johal B, Pearl LH, Neely R, Keep NH, Watts FZ, Morris JR.

Nat Struct Mol Biol. 2016 Jul;23(7):647-55. doi: 10.1038/nsmb.3236. Epub 2016 May 30.


Mode of action of DNA-competitive small molecule inhibitors of tyrosyl DNA phosphodiesterase 2.

Hornyak P, Askwith T, Walker S, Komulainen E, Paradowski M, Pennicott LE, Bartlett EJ, Brissett NC, Raoof A, Watson M, Jordan AM, Ogilvie DJ, Ward SE, Atack JR, Pearl LH, Caldecott KW, Oliver AW.

Biochem J. 2016 Jul 1;473(13):1869-79. doi: 10.1042/BCJ20160180. Epub 2016 Apr 20.


The Ku-binding motif is a conserved module for recruitment and stimulation of non-homologous end-joining proteins.

Grundy GJ, Rulten SL, Arribas-Bosacoma R, Davidson K, Kozik Z, Oliver AW, Pearl LH, Caldecott KW.

Nat Commun. 2016 Apr 11;7:11242. doi: 10.1038/ncomms11242.


Review: The HSP90 molecular chaperone-an enigmatic ATPase.

Pearl LH.

Biopolymers. 2016 Aug;105(8):594-607. doi: 10.1002/bip.22835. Review.


DNA repair, genome stability and cancer: a historical perspective.

Jeggo PA, Pearl LH, Carr AM.

Nat Rev Cancer. 2016 Jan;16(1):35-42. doi: 10.1038/nrc.2015.4. Epub 2015 Dec 15. Review.


ATM Localization and Heterochromatin Repair Depend on Direct Interaction of the 53BP1-BRCT2 Domain with γH2AX.

Baldock RA, Day M, Wilkinson OJ, Cloney R, Jeggo PA, Oliver AW, Watts FZ, Pearl LH.

Cell Rep. 2015 Dec 15;13(10):2081-9. doi: 10.1016/j.celrep.2015.10.074. Epub 2015 Nov 25.


Corrigendum: The zinc-finger domains of PARP1 cooperate to recognize DNA strand breaks.

Ali AA, Timinszky G, Arribas-Bosacoma R, Kozlowski M, Hassa PO, Hassler M, Ladurner AG, Pearl LH, Oliver AW.

Nat Struct Mol Biol. 2015 Aug;22(8):645. doi: 10.1038/nsmb0815-645a. No abstract available.


Tah1 helix-swap dimerization prevents mixed Hsp90 co-chaperone complexes.

Morgan RM, Pal M, Roe SM, Pearl LH, Prodromou C.

Acta Crystallogr D Biol Crystallogr. 2015 May;71(Pt 5):1197-206. doi: 10.1107/S1399004715004551. Epub 2015 Apr 25.


Computational Modeling for Language Acquisition: A Tutorial With Syntactic Islands.

Pearl LS, Sprouse J.

J Speech Lang Hear Res. 2015 Jun;58(3):740-53. doi: 10.1044/2015_JSLHR-L-14-0362.


Therapeutic opportunities within the DNA damage response.

Pearl LH, Schierz AC, Ward SE, Al-Lazikani B, Pearl FM.

Nat Rev Cancer. 2015 Mar;15(3):166-80. doi: 10.1038/nrc3891. Review.


The Utility of Cognitive Plausibility in Language Acquisition Modeling: Evidence From Word Segmentation.

Phillips L, Pearl L.

Cogn Sci. 2015 Nov;39(8):1824-54. doi: 10.1111/cogs.12217. Epub 2015 Feb 6.


Structural basis for phosphorylation-dependent recruitment of Tel2 to Hsp90 by Pih1.

Pal M, Morgan M, Phelps SE, Roe SM, Parry-Morris S, Downs JA, Polier S, Pearl LH, Prodromou C.

Structure. 2014 Jun 10;22(6):805-18. doi: 10.1016/j.str.2014.04.001. Epub 2014 May 1.


Development of an oligonucleotide-based fluorescence assay for the identification of tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors.

Walker S, Meisenberg C, Bibby RA, Askwith T, Williams G, Rininsland FH, Pearl LH, Oliver AW, El-Khamisy S, Ward S, Atack JR.

Anal Biochem. 2014 Jun 1;454:17-22. doi: 10.1016/j.ab.2014.03.004. Epub 2014 Mar 14.


Restricting direct interaction of CDC37 with HSP90 does not compromise chaperoning of client proteins.

Smith JR, de Billy E, Hobbs S, Powers M, Prodromou C, Pearl L, Clarke PA, Workman P.

Oncogene. 2015 Jan 2;34(1):15-26. doi: 10.1038/onc.2013.519. Epub 2013 Dec 2.


A mechanism for the inhibition of DNA-PK-mediated DNA sensing by a virus.

Peters NE, Ferguson BJ, Mazzon M, Fahy AS, Krysztofinska E, Arribas-Bosacoma R, Pearl LH, Ren H, Smith GL.

PLoS Pathog. 2013;9(10):e1003649. doi: 10.1371/journal.ppat.1003649. Epub 2013 Oct 3.


Phosphorylation-dependent assembly and coordination of the DNA damage checkpoint apparatus by Rad4(TopBP1).

Qu M, Rappas M, Wardlaw CP, Garcia V, Ren JY, Day M, Carr AM, Oliver AW, Du LL, Pearl LH.

Mol Cell. 2013 Sep 26;51(6):723-736. doi: 10.1016/j.molcel.2013.08.030.


The BAH domain of Rsc2 is a histone H3 binding domain.

Chambers AL, Pearl LH, Oliver AW, Downs JA.

Nucleic Acids Res. 2013 Oct;41(19):9168-82. doi: 10.1093/nar/gkt662. Epub 2013 Jul 31.


ATP-competitive inhibitors block protein kinase recruitment to the Hsp90-Cdc37 system.

Polier S, Samant RS, Clarke PA, Workman P, Prodromou C, Pearl LH.

Nat Chem Biol. 2013 May;9(5):307-12. doi: 10.1038/nchembio.1212. Epub 2013 Mar 17. Erratum in: Nat Chem Biol. 2013 Jun;9(6):406.


3,6-Diamino-4-(2-halophenyl)-2-benzoylthieno[2,3-b]pyridine-5-carbonitriles are selective inhibitors of Plasmodium falciparum glycogen synthase kinase-3.

Fugel W, Oberholzer AE, Gschloessl B, Dzikowski R, Pressburger N, Preu L, Pearl LH, Baratte B, Ratin M, Okun I, Doerig C, Kruggel S, Lemcke T, Meijer L, Kunick C.

J Med Chem. 2013 Jan 10;56(1):264-75. doi: 10.1021/jm301575n. Epub 2012 Dec 27.


Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B.

Tahtouh T, Elkins JM, Filippakopoulos P, Soundararajan M, Burgy G, Durieu E, Cochet C, Schmid RS, Lo DC, Delhommel F, Oberholzer AE, Pearl LH, Carreaux F, Bazureau JP, Knapp S, Meijer L.

J Med Chem. 2012 Nov 8;55(21):9312-30. doi: 10.1021/jm301034u. Epub 2012 Oct 8.


The zinc-finger domains of PARP1 cooperate to recognize DNA strand breaks.

Ali AAE, Timinszky G, Arribas-Bosacoma R, Kozlowski M, Hassa PO, Hassler M, Ladurner AG, Pearl LH, Oliver AW.

Nat Struct Mol Biol. 2012 Jun 10;19(7):685-692. doi: 10.1038/nsmb.2335. Erratum in: Nat Struct Mol Biol. 2015 Aug;22(8):645.


Engineering human MEK-1 for structural studies: A case study of combinatorial domain hunting.

Meier C, Brookings DC, Ceska TA, Doyle C, Gong H, McMillan D, Saville GP, Mushtaq A, Knight D, Reich S, Pearl LH, Powell KA, Savva R, Allen RA.

J Struct Biol. 2012 Feb;177(2):329-34. doi: 10.1016/j.jsb.2012.01.002. Epub 2012 Jan 8.


Visualization of a DNA-PK/PARP1 complex.

Spagnolo L, Barbeau J, Curtin NJ, Morris EP, Pearl LH.

Nucleic Acids Res. 2012 May;40(9):4168-77. doi: 10.1093/nar/gkr1231. Epub 2012 Jan 5.


The structural basis for substrate recognition by mammalian polynucleotide kinase 3' phosphatase.

Garces F, Pearl LH, Oliver AW.

Mol Cell. 2011 Nov 4;44(3):385-96. doi: 10.1016/j.molcel.2011.08.036.


Targeting the Hsp90 molecular chaperone with novel macrolactams. Synthesis, structural, binding, and cellular studies.

Day JE, Sharp SY, Rowlands MG, Aherne W, Hayes A, Raynaud FI, Lewis W, Roe SM, Prodromou C, Pearl LH, Workman P, Moody CJ.

ACS Chem Biol. 2011 Dec 16;6(12):1339-47. doi: 10.1021/cb200196e. Epub 2011 Oct 4.


Features of the Streptomyces hygroscopicus HtpG reveal how partial geldanamycin resistance can arise with mutation to the ATP binding pocket of a eukaryotic Hsp90.

Millson SH, Chua CS, Roe SM, Polier S, Solovieva S, Pearl LH, Sim TS, Prodromou C, Piper PW.

FASEB J. 2011 Nov;25(11):3828-37. doi: 10.1096/fj.11-188821. Epub 2011 Jul 21.


The crystal structure of yeast CCT reveals intrinsic asymmetry of eukaryotic cytosolic chaperonins.

Dekker C, Roe SM, McCormack EA, Beuron F, Pearl LH, Willison KR.

EMBO J. 2011 Jun 24;30(15):3078-90. doi: 10.1038/emboj.2011.208.


Regulation of DNA replication through Sld3-Dpb11 interaction is conserved from yeast to humans.

Boos D, Sanchez-Pulido L, Rappas M, Pearl LH, Oliver AW, Ponting CP, Diffley JF.

Curr Biol. 2011 Jul 12;21(13):1152-7. doi: 10.1016/j.cub.2011.05.057. Epub 2011 Jun 23.


p185, an immunodominant epitope, is an autoantigen mimotope.

Kumar S, Hinks JA, Maman J, Ravirajan CT, Pearl LH, Isenberg DA.

J Biol Chem. 2011 Jul 22;286(29):26220-7. doi: 10.1074/jbc.M111.224303. Epub 2011 May 12.


Evidence for a remodelling of DNA-PK upon autophosphorylation from electron microscopy studies.

Morris EP, Rivera-Calzada A, da Fonseca PC, Llorca O, Pearl LH, Spagnolo L.

Nucleic Acids Res. 2011 Jul;39(13):5757-67. doi: 10.1093/nar/gkr146. Epub 2011 Mar 30.

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