Browsing by author "Pearl, Laurence"
Now showing items 1-20 of 20
-
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; et al. (CELL PRESS, 2015-12-15)53BP1 plays multiple roles in mammalian DNA damage repair, mediating pathway choice and facilitating DNA double-strand break repair in heterochromatin. Although it possesses a C-terminal BRCT2 domain, commonly involved in ... -
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; et al. (ELIFE SCIENCES PUBLICATIONS LTD, 2018-10-08)TOPBP1 and its fission yeast homologueRad4, are critical players in a range of DNA replication, repair and damage signalling processes. They are composed of multiple BRCT domains, some of which bind phosphorylated motifs ... -
Differential Regulation of G1 CDK Complexes by the Hsp90-Cdc37 Chaperone System
Hallett, ST; Pastok, MW; Morgan, RML; Wittner, A; Blundell, KLIM; et al. (Elsevier BV, 2017-10-01) -
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; et al. (Elsevier BV, 2019-01-01) -
HECTD3 Mediates an HSP90-Dependent Degradation Pathway for Protein Kinase Clients
Li, Z; Zhou, L; Prodromou, C; Savic, V; Pearl, LH (Elsevier BV, 2017-06-01) -
HSP90-CDC37-PP5 forms a structural platform for kinase dephosphorylation.
Oberoi, J; Guiu, XA; Outwin, EA; Schellenberger, P; Roumeliotis, TI; et al. (NATURE PORTFOLIO, 2022-11-29)Activation of client protein kinases by the HSP90 molecular chaperone system is affected by phosphorylation at multiple sites on HSP90, the kinase-specific co-chaperone CDC37, and the kinase client itself. Removal of ... -
MDC1 Interacts with TOPBP1 to Maintain Chromosomal Stability during Mitosis.
Leimbacher, P-A; Jones, SE; Shorrocks, A-MK; de Marco Zompit, M; Day, M; et al. (CELL PRESS, 2019-05-02)In mitosis, cells inactivate DNA double-strand break (DSB) repair pathways to preserve genome stability. However, some early signaling events still occur, such as recruitment of the scaffold protein MDC1 to phosphorylated ... -
MoKCa database--mutations of kinases in cancer.
Richardson, CJ; Gao, Q; Mitsopoulous, C; Zvelebil, M; Pearl, LH; et al. (OXFORD UNIV PRESS, 2009-01-01)Members of the protein kinase family are amongst the most commonly mutated genes in human cancer, and both mutated and activated protein kinases have proved to be tractable targets for the development of new anticancer ... -
PARP3 is a sensor of nicked nucleosomes and monoribosylates histone H2B(Glu2).
Grundy, GJ; Polo, LM; Zeng, Z; Rulten, SL; Hoch, NC; et al. (Springer Science and Business Media LLC, 2016-08-17)PARP3 is a member of the ADP-ribosyl transferase superfamily that we show accelerates the repair of chromosomal DNA single-strand breaks in avian DT40 cells. Two-dimensional nuclear magnetic resonance experiments reveal ... -
Phosphorylation-dependent assembly of DNA damage response systems and the central roles of TOPBP1.
Day, M; Oliver, AW; Pearl, LH (ELSEVIER, 2021-10-19)The cellular response to DNA damage (DDR) that causes replication collapse and/or DNA double strand breaks, is characterised by a massive change in the post-translational modifications (PTM) of hundreds of proteins involved ... -
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; et al. (ELIFE SCIENCES PUBLICATIONS LTD, 2019-05-28)Coordination of the cellular response to DNA damage is organised by multi-domain 'scaffold' proteins, including 53BP1 and TOPBP1, which recognise post-translational modifications such as phosphorylation, methylation and ... -
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; et al. (NATURE PUBLISHING GROUP, 2015-01-02)The HSP90 molecular chaperone plays a key role in the maturation, stability and activation of its clients, including many oncogenic proteins. Kinases are a substantial and important subset of clients requiring the key ... -
Review: The HSP90 molecular chaperone—an enigmatic ATPase
Pearl, LH (Wiley, 2016-08-01)<jats:title>ABSTRACT</jats:title><jats:p>The HSP90 molecular chaperone is involved in the activation and cellular stabilization of a range of ‘client’ proteins, of which oncogenic protein kinases and nuclear steroid hormone ... -
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; et al. (Springer Science and Business Media LLC, 2018-04-16)The R2TP/Prefoldin-like co-chaperone, in concert with HSP90, facilitates assembly and cellular stability of RNA polymerase II, and complexes of PI3-kinase-like kinases such as mTOR. However, the mechanism by which this ... -
Solution structure of the Hop TPR2A domain and investigation of target druggability by NMR, biochemical and in silico approaches.
Darby, JF; Vidler, LR; Simpson, PJ; Al-Lazikani, B; Matthews, SJ; et al. (NATURE PORTFOLIO, 2020-09-29)Heat shock protein 90 (Hsp90) is a molecular chaperone that plays an important role in tumour biology by promoting the stabilisation and activity of oncogenic 'client' proteins. Inhibition of Hsp90 by small-molecule drugs, ... -
Structural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus.
Rivera-Calzada, A; Arribas-Bosacoma, R; Ruiz-Ramos, A; Escudero-Bravo, P; Boskovic, J; et al. (NATURE PORTFOLIO, 2022-11-18)Detection of cytosolic DNA is a central element of the innate immunity system against viral infection. The Ku heterodimer, a component of the NHEJ pathway of DNA repair in the nucleus, functions as DNA sensor that detects ... -
Structure of the human RAD17-RFC clamp loader and 9-1-1 checkpoint clamp bound to a dsDNA-ssDNA junction.
Day, M; Oliver, AW; Pearl, LH (OXFORD UNIV PRESS, 2022-08-12)The RAD9-RAD1-HUS1 (9-1-1) clamp forms one half of the DNA damage checkpoint system that signals the presence of substantial regions of single-stranded DNA arising from replication fork collapse or resection of DNA double ... -
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; et al. (NATURE PUBLISHING GROUP, 2016-04-11)The Ku-binding motif (KBM) is a short peptide module first identified in APLF that we now show is also present in Werner syndrome protein (WRN) and in Modulator of retrovirus infection homologue (MRI). We also identify a ... -
TopBP1 utilises a bipartite GINS binding mode to support genome replication.
Day, M; Tetik, B; Parlak, M; Almeida-Hernández, Y; Räschle, M; et al. (NATURE PORTFOLIO, 2024-02-27)Activation of the replicative Mcm2-7 helicase by loading GINS and Cdc45 is crucial for replication origin firing, and as such for faithful genetic inheritance. Our biochemical and structural studies demonstrate that the ... -
Uncovering an allosteric mode of action for a selective inhibitor of human Bloom syndrome protein.
Chen, X; Ali, YI; Fisher, CE; Arribas-Bosacoma, R; Rajasekaran, MB; et al. (eLife Sciences Publications, Ltd, 2021-03-01)BLM (Bloom syndrome protein) is a RECQ-family helicase involved in the dissolution of complex DNA structures and repair intermediates. Synthetic lethality analysis implicates BLM as a promising target in a range of cancers ...