Pearl Lab


Selections from more than 157 peer-reviewed publications 2001-2022

Professor Laurence Pearl FRS FMedSci MAE

Oberoi,J., Aran-Guiu,X., Outwin,E.A., Schellenberger,P., Roumeliotis,T.I, Choudhary,J.S., and Pearl,L.H. (2022) ‘HSP90-CDC37-PP5 forms a structural platform for kinase dephosphorylation’, Nature Commun., 13:7343.

Rivera-Calzada,A. Arribas-Bosacoma,R., Ruiz-Ramos,A., Escudero-Bravo,P., Boskovic,J., Fernandez-Leiro,R, Oliver,A.W., Pearl,L.H. and Llorca,O. (2022) ‘Structural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus’, Nature Commun., 13:7062.

Day,M., Oliver,A.W. and Pearl LH. (2022) ‘Structure of the human RAD17-RFC clamp loader and 9-1-1 checkpoint clamp bound to a dsDNA-ssDNA junction’, Nucleic Acids Res. 50:8279-8289.

Pal,M., Muñoz-Hernandez,H., Bjorklund,D., Zhou,L., Degliesposti,G., Skehel,J.M., Hesketh, E.L., Thompson,R.F., Pearl,L.H., Llorca,O. and Prodromou,C. (2021) ‘Structure of the TELO2-TTI1-TTI2 complex and its function in TOR recruitment to the R2TP chaperone’, Cell Rep., 36:109317.

Day,M., Morris,S.P., Houghton-Gisby,J., Oliver,A.W. and Pearl,L.H. (2021) ‘Structural basis for recruitment of the CHK1 DNA damage kinase by the CLASPIN scaffold protein’, Structure, 29,531-539.

Chen,X., Ali,Y.I., Fisher,C.E.L., Arribas-Bosacoma,R., Rajasekaran,M.B., Williams,G., Walker,S., Booth,J.R., Hudson,J.J.R. Roe,S.M., Pearl,L.H., Ward,S.E., Pearl,F.M.G and Oliver,A.W. (2021) ‘Uncovering an allosteric mode of action for a selective inhibitor of human Bloom syndrome protein’, eLife, 10:e65339.

Bigot,N., Day,M., Baldock,R.A., Watts,F.Z., Oliver,A.W. and Pearl,L.H.(2019) ‘Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1 to control the G1 DNA damage checkpoint’, eLife, 8,e44353.

Muñoz-Hernández,H., Pal,M., Rodríguez,C.F., Fernandez-Leiro,R., Prodromou,C., Pearl,L.H.and Llorca,O. (2019) ‘Mechanism of remodeling and nucleotide-exchange of RUVBL1-RUVBL2 ATPases in the R2TP co-chaperone’, Science Adv., 5, eaaw1616

Leimbacher,P.-A., Jones,S.E., Shorrocks,A.-M.K., de Marco Zompit,M., Day,M., Blaauwendraad,J., Bundschuh,D., Bonham,S., Fischer,R., Fink,D., Kessler,B.M., Oliver,A.W., Pearl,L.H., Blackford,A.N., and Stucki,M. (2019) ‘MDC1 interacts with TOPBP1 to maintain chromosomal stability during mitosis’, Mol. Cell, 74, 571-583.

Polo,L.M., Xu,Y., Hornyak,P., Garces,F., Zeng,Z., Hailstone,R., Matthews,S.J., Caldecott,K.W., Oliver,A.W. and Pearl,L.H.(2019) ‘Efficient single strand break repair requires binding to both poly(ADP-ribose) and DNA by the central BRCT domain of XRCC1’, Cell Rep, 26,573-581.

Day,M., Rappas,M., PtasiƄska, K., Boos,D., Oliver,A.W. and Pearl,L.H.(2018) ‘BRCT domains of the DNA damage checkpoint proteins TOPBP1/Rad4 display distinct specificities for phosphopeptide ligands’, eLife7:e39979.

Martino,F., Pal,M., Muñoz-Hernández,H., Rodríguez,C.F., Núñez-Ramírez,R., Gil-Carton,D., Degliesposti,G., Skehel,J.M., Roe,S.M., Prodromou,C., Pearl,L.H.and Llorca,O. (2018) ‘RPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co-chaperone complex’,Nature Commun., 9:3063.

Li,Z., Zhou,L., Prodromou,C., Savic,V. and Pearl,L.H.(2017), ‘HECTD3 mediates an HSP90-dependent degradation pathway for protein kinase clients’,Cell Rep.,19. 2515-2528.

Rivera-Calzada,A., Pal,M., Muñoz-Hernandez,H. Luque-Ortega,J.R., Gil-Carton,D. Degliesposti,G., Skehel,J.M., Prodromou,C., Pearl,L.H.and Llorca,O. (2017) ‘The structure of the R2TP complex defines a platform for recruiting diverse client proteins to the HSP90 molecular chaperone system’, Structure, 25,1145-1152.

Grundy,G.J., Polo,L.M., Zeng,Z., Rulten,S.L.,, Hoch,N.C., Paomephan,P., Xu,Y., Sweet,S., Thorne,A., Oliver,A.W., Matthews,S.J., Pearl,L.H.and Caldecott,K.W. (2016) ‘PARP3 is a sensor of nicked nucleosomes and monoribosylates histone H2BGlu2’, Nature Commun., 7:12404.

Schulze,A., Beliu,G., Helmerich,D.A., Schubert,J., Pearl,L.H., Prodromou,C. and Neuweiler,H. (2016) ‘Cooperation of local motions in the Hsp90 molecular chaperone ATPase mechanism’, Nature Chem. Biol., 12, 628-635.

Baldock, R.A., Day,M., Wilkinson,O.J., Cloney,R., Jeggo,P.A., Oliver,A.W., Watts,F.Z. and Pearl,L.H.(2015) ‘ATM localisation and heterochromatin repair depend on direct interaction of the 53BP1-BRCT2 domain with gH2AX’, Cell Rep., 13, 2081-2089.

Pal,M., Morgan,R.M., Phelps,S.E.L., Roe,S.M., Parry-Morris,S., Downs,J.A., Polier,S., Pearl,L.H.and Prodromou,C. (2014) ‘Structural basis for phosphorylation-dependent recruitment of Tel2 to Hsp90 by Pih1’, Structure, 22, 805-818.

Qu, M., Rappas, M., Wardlaw,C.P., Garcia,V., Ren,J.-Y., Day,M., Carr,A.M., Oliver,A.W., Du,L.-L. and Pearl,L.H. (2013), ‘Phosphorylation-dependent Assembly and Coordination of the DNA Damage Checkpoint Apparatus by Rad4TopBP1’, Mol. Cell, 51, 723–736.

Polier,S., Samant,R.S., Clarke,P.A., Workman,P., Prodromou,C. and Pearl,L.H. (2013), ‘ATP-competitive inhibitors of protein kinases block recruitment to the Hsp90-Cdc37 system’, Nature Chem Biol., 9, 307-312..

Ali.A.E.A., Timinszky,G., Arribas-Bosacoma,R., Kozlowski, M., Hassa,P.O., Hassler,M., Ladurner,A.G., Pearl,L.H. and Oliver,A.W. (2012) ‘The zinc-finger domains of PARP1 cooperate to recognize DNA strand breaks’, Nature Struct. Mol. Biol., 19, 685-692.

Garcas, F., Pearl, L.H. and Oliver, A.W. (2011) ‘The structural basis for substrate recognition by mammalian polynucleotide kinase 3’ phosphatase’, Mol Cell, 44, 385-396

Mollapour,M., Tsutsumi,S., Truman,A.W., Xu,W., Vaughan,C.K., Beebe,K., Konstantinova,A., Vourganti,S., Panaretou,B., Piper,P.W., Trepel,J.B., Prodromou,C., Pearl,L.H. and Neckers,L. (2011) 'Threonine 22 phosphorylation attenuates hsp90 interaction with cochaperones and affects its chaperone activity', Mol. Cell, 41, 672-681

Ali,M.M.U., Bagratuni,T., Davenport,E.L., Nowak,P.R., Silva-Santisteban,M.C., Hardcastle,A., McAndrews,C., Rowlands,M.G., Morgan,G.J., Aherne,W., Collins,I., Davies,F.E. and Pearl,L.H. (2011) ‘Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response’, EMBO J., 30, 894-905.

Zhang, M., Kadota, Y., Prodromou, C., Shirasu, K. and Pearl, L.H. (2010) ‘Structural basis for assembly of Hsp90-Sgt1-CHORD protein complexes: implications for chaperoning of NLR innate immunity receptors’, Mol. Cell, 39, 269-281

Oliver,A.W., Swift,S., Lord,C.J., AshworthA. and Pearl,L.H. (2009) 'Structural Basis for Recruitment of BRCA2 by PALB2', EMBO Rep., 10, 990-996.

Doré,A.S., Kilkenny,M.L., Rzechorzek,N.J. and Pearl,L.H. (2009) 'Crystal Structure of the Rad9-Rad1-Hus1 DNA Damage Checkpoint Complex - Implications for Clamp Loading and Regulation', Mol. Cell, 34, 735-745.

Vaughan,C.K., Mollapour,M., Smith,J.R., Truman,A., Hu,B., Good,V.M., Panaretou,B., Neckers,L., Clarke,P.A., Workman,P., Piper,P.W., Prodromou,C. and Pearl,L.H. (2008) 'Hsp90-dependent activation of protein kinases is regulated by chaperone-targeted dephosphorylation of Cdc37', Mol. Cell, 31, 886-895.

Vaughan,C.K., Gohlke,U., Sobot,F., Robinson,C.V., Ali,M.M.U., Prodromou,C., Saibil,H.R. and Pearl,L.H. (2006) 'Structure of an Hsp90 - Cdc37 - Cdk4 complex', Mol. Cell, 29, 697-707.

Oliver,A.W., Paul,A., Boxall,K.J., Barrie,S.E., Aherne,G.W., Garrett,M.D., Mittnacht,S. and Pearl,L.H. (2006) 'Trans-activation of the DNA damage-signalling protein kinase Chk2 by T-loop exchange'. EMBO J, 25, 3179-3190.

Spagnolo,L., Rivera-Calzada,A., Pearl,L.H. and Llorca,O. (2006) 'Three-dimensional structure of the human DNA-PKcs/Ku70/Ku80 complex assembled on DNA and its implications for DNA double-strand break repair', Mol. Cell, 22, 511-519.

Ali,M.M.U., Roe,S.M., Vaughan.C.K., Meyer,P., Panaretou,B., Piper,P.W., Prodromou,C. and Pearl,L.H. (2006) 'Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex', Nature, 440, 1013-1017.

Zhang,M., Windheim,M., Roe,S.M., Peggie,M., Cohen,P., Prodromou,C. and Pearl,L.H. (2005) 'Chaperoned ubiquitylation - Crystal structures of the CHIP U-box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex', Mol. Cell, 20, 525-538.

Roe, S.M., M.M.U. Ali, Meyer, M., Vaughan, C.K., Panaretou, B., Piper, P.W., Prodromou, C. and Pearl, L.H. (2004) 'The mechanism of Hsp90 regulation by the protein kinase-specific co-chaperone p50cdc37', Cell, 116, 87-98.

Dajani, R., Fraser,E., Roe,S.M., Young,N., Good,V., Dale,T.C. and Pearl,L.H. (2001) 'Crystal structure of glycogen synthase kinase 3b : Structural basis for phosphate-primed substrate specificity and auto-inhibition', Cell 105, 721-732.

Publications with abstracts and links