Imperial College London

ProfessorPaulFreemont

Faculty of MedicineDepartment of Medicine

Chair in Protein Crystallography
 
 
 
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Contact

 

+44 (0)20 7594 5327p.freemont

 
 
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Location

 

259Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

246 results found

Morera S, Imberty A, Aschke-Sonnenborn U, Ruger W, Freemont PSet al., 1999, T4 phage beta-glucosyltransferase: Substrate binding and proposed catalytic mechanism, JOURNAL OF MOLECULAR BIOLOGY, Vol: 292, Pages: 717-730, ISSN: 0022-2836

JOURNAL ARTICLE

Imberty A, Monier C, Bettler E, Morera S, Freemont P, Sippl M, Flockner H, Ruger W, Breton Cet al., 1999, Fold recognition study of alpha 3-galactosyltransferase and molecular modeling of the nucleotide sugar-binding domain, GLYCOBIOLOGY, Vol: 9, Pages: 713-722, ISSN: 0959-6658

JOURNAL ARTICLE

Karow JK, Newman RH, Freemont PS, Hickson IDet al., 1999, Oligomeric ring structure of the Bloom's syndrome helicase, CURRENT BIOLOGY, Vol: 9, Pages: 597-600, ISSN: 0960-9822

JOURNAL ARTICLE

Lu PJ, Sundquist K, Baeckstrom D, Poulsom R, Hanby A, Meier-Ewert S, Jones T, Mitchell M, Pitha-Rowe P, Freemont P, Taylor-Papadimitriou Jet al., 1999, A novel gene (PLU-1) containing highly conserved putative DNA chromatin binding motifs is specifically up-regulated in breast cancer, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 274, Pages: 15633-15645, ISSN: 0021-9258

JOURNAL ARTICLE

Soulez M, Saurin AJ, Freemont PS, Knight JCet al., 1999, SSX and the synovial-sarcoma-specific chimaeric protein SYT-SSX co-localize with the human Polycomb group complex, ONCOGENE, Vol: 18, Pages: 2739-2746, ISSN: 0950-9232

JOURNAL ARTICLE

Assier E, Bouzinba-Segard H, Stolzenberg MC, Stephens R, Bardos J, Freemont P, Charron D, Trowsdale J, Rich Tet al., 1999, Isolation, sequencing and expression of RED, a novel human gene encoding an acidic-basic dipeptide repeat, GENE, Vol: 230, Pages: 145-154, ISSN: 0378-1119

JOURNAL ARTICLE

Allford S, Grimwade D, Langabeer S, Duprez E, Saurin A, Chatters S, Walker H, Roberts P, Rogers J, Bain B, Patterson K, McKernan A, Freemont P, Solomon E, Burnett A, Goldstone A, Linch Det al., 1999, Identification of the t(15;17) in AML FAB types other than M3: evaluation of the role of molecular screening for the PML/RAR alpha rearrangement in newly diagnosed AML, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 105, Pages: 198-207, ISSN: 0007-1048

JOURNAL ARTICLE

Allford S, Grimwade D, Langabeer S, Duprez E, Saurin A, Chatters S, Walker H, Roberts P, Rogers J, Bain B, Patterson K, McKernan A, Freemont P, Solomon E, Burnett A, Goldstone A, Linch Det al., 1999, Identification of the t(15;17) in AML FAB types other than M3: evaluation of the role of molecular screening for the PML/RARalpha rearrangement in newly diagnosed AML. The Medical Research Council (MRC) Adult Leukaemia Working Party., Br J Haematol, Vol: 105, Pages: 198-207, ISSN: 0007-1048

Acute promyelocytic leukaemia (APL) is characterized by the t(15;17) leading to the formation of PML-RARalpha and RARalpha-PML fusion genes; this rearrangement has been considered both diagnostic for, and restricted to, this subtype of acute myeloid leukaemia (AML FAB M3). We describe two cases of AML with the t(15;17) associated with a PML/RARalpha rearrangement which lacked typical APL morphology, classified as FAB M1 and M2 respectively. In both cases morphological review revealed small populations of cells which exhibited some features associated with APL. In the case classified as M1, PML immunofluorescence studies revealed the classic microparticulate nuclear staining pattern as observed in typical cases of APL with the t(15;17). Similarly, blasts from this case were found to be sensitive to ATRA in vitro as determined by NBT reduction test and by normalization of the PML nuclear body staining pattern. To determine the frequency of PML/RARalpha rearrangements in FAB subtypes other than M3, 530 patients from the MRC AML trials were screened using nested RT-PCR. Only one individual, initially classified as M5 with a normal karyotype, was found to have a PML/RARalpha rearrangement. The diagnosis was revised to M3 variant on subsequent morphological review. In conclusion, this study demonstrates that, in rare cases, the t(15;17) is not restricted to patients with M3 morphology as defined by current FAB criteria. Therefore, although we consider cytogenetic analysis of newly diagnosed cases of AML to be mandatory, our data suggests that routine molecular screening for PML/RARalpha rearrangements is not justified and should be reserved for those cases displaying features which may be suspicious of APL even if such cells comprise only a minority of the total population.

JOURNAL ARTICLE

Duprez E, Saurin AJ, Desterro JM, Lallemand-Breitenbach V, Howe K, Boddy MN, Solomon E, de The H, Hay RT, Freemont PSet al., 1999, SUMO-1 modification of the acute promyelocytic leukaemia protein PML: implications for nuclear localisation, JOURNAL OF CELL SCIENCE, Vol: 112, Pages: 381-393, ISSN: 0021-9533

JOURNAL ARTICLE

Bates PA, Dokurno P, Freemont PS, Sternberg MJEet al., 1998, Conformational analysis of the first observed non-proline cis-peptide bond occurring within the complementarity determining region (CDR) of an antibody, JOURNAL OF MOLECULAR BIOLOGY, Vol: 284, Pages: 549-555, ISSN: 0022-2836

JOURNAL ARTICLE

Dokurno P, Bates PA, Band HA, Stewart LMD, Lally JM, Burchell JM, Taylor-Papadimitriou J, Snary D, Sternberg MJE, Freemont PSet al., 1998, Crystal structure at 1.95 angstrom resolution of the breast tumour-specific antibody SM3 complexed with its peptide epitope reveals novel hypervariable loop recognition, JOURNAL OF MOLECULAR BIOLOGY, Vol: 284, Pages: 713-728, ISSN: 0022-2836

JOURNAL ARTICLE

Zhang XD, Morera S, Bates PA, Whitehead PC, Coffer AI, Hainbucher K, Nash RA, Sternberg MJE, Lindahl T, Freemont PSet al., 1998, Structure of an XRCC1 BRCT domain: a new protein-protein interaction module, EMBO JOURNAL, Vol: 17, Pages: 6404-6411, ISSN: 0261-4189

JOURNAL ARTICLE

Hodges M, Tissot C, Freemont PS, 1998, Protein regulation: Tag wrestling with relatives of ubiquitin, CURRENT BIOLOGY, Vol: 8, Pages: R749-R752, ISSN: 0960-9822

JOURNAL ARTICLE

Saurin AJ, Shiels C, Williamson J, Satijn DPE, Otte AP, Sheer D, Freemont PSet al., 1998, The human polycomb group complex associates with pericentromeric heterochromatin to form a novel nuclear domain, Journal of Cell Biology, Vol: 142, Pages: 887-898, ISSN: 0021-9525

The Polycomb group (PcG) complex is a chromatin-associated multiprotein complex, involved in the stable repression of homeotic gene activity in Drosophila. Recently, a mammalian PcG complex has been identified with several PcG proteins implicated in the regulation of Hox gene expression. Although the mammalian PcG complex appears analogous to the complex in Drosophila, the molecular mechanisms and functions for the mammalian PcG complex remain unknown. Here we describe a detailed characterization of the human PcG complex in terms of cellular localization and chromosomal association. By using antibodies that specifically recognize three human PcG proteins— RING1, BMI1, and hPc2—we demonstrate in a number of human cell lines that the PcG complex forms a unique discrete nuclear structure that we term PcG bodies. PcG bodies are prominent novel nuclear structures with the larger PcG foci generally localized near the centromeres, as visualized with a kinetochore antibody marker. In both normal fetal and adult fibroblasts, PcG bodies are not randomly dispersed, but appear clustered into defined areas within the nucleus. We show in three different human cell lines that the PcG complex can tightly associate with large pericentromeric heterochromatin regions (1q12) on chromosome 1, and with related pericentromeric sequences on different chromosomes, providing evidence for a mammalian PcG–heterochromatin association. Furthermore, these heterochromatin-bound PcG complexes remain stably associated throughout mitosis, thereby allowing the potential inheritance of the PcG complex through successive cell divisions. We discuss these results in terms of the known function of the PcG complex as a transcriptional repression complex.

JOURNAL ARTICLE

Hodges M, Tissot C, Howe K, Grimwade D, Freemont PSet al., 1998, Structure, organization, and dynamics of promyelocytic leukemia protein nuclear bodies, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 63, Pages: 297-304, ISSN: 0002-9297

JOURNAL ARTICLE

Everett RD, Freemont P, Saitoh H, Dasso M, Orr A, Kathoria M, Parkinson Jet al., 1998, The disruption of ND10 during herpes simplex virus infection correlates with the Vmw11O- and proteasome-dependent loss of several PML isoforms, JOURNAL OF VIROLOGY, Vol: 72, Pages: 6581-6591, ISSN: 0022-538X

JOURNAL ARTICLE

Lally JM, Newman RH, Knowles PP, Islam S, Coffer AI, Parker M, Freemont PSet al., 1998, Crystallization of an intact GST-estrogen receptor hormone binding domain fusion protein, ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, Vol: 54, Pages: 423-426, ISSN: 0907-4449

JOURNAL ARTICLE

Cao TY, Duprez E, Borden KLB, Freemont PS, Etkin LDet al., 1998, Ret finger protein is a normal component of PML nuclear bodies and interacts directly with PML, JOURNAL OF CELL SCIENCE, Vol: 111, Pages: 1319-1329, ISSN: 0021-9533

JOURNAL ARTICLE

Rabouille C, Kondo H, Newman R, Hui N, Freemont P, Warren Get al., 1998, Syntaxin 5 is a common component of the NSF- and p97-mediated reassembly pathways of Golgi cisternae from mitotic Golgi fragments in vitro, CELL, Vol: 92, Pages: 603-610, ISSN: 0092-8674

JOURNAL ARTICLE

Saha V, Young BD, Freemont PS, 1998, Translocations, fusion genes, and acute leukemia, JOURNAL OF CELLULAR BIOCHEMISTRY, Pages: 264-+, ISSN: 0730-2312

JOURNAL ARTICLE

Howe K, Williamson J, Boddy N, Sheer D, Freemont P, Solomon Eet al., 1998, The ubiquitin-homology gene PIC1: Characterization of mouse (Pic1) and human (UBL1) genes and pseudogenes, GENOMICS, Vol: 47, Pages: 92-100, ISSN: 0888-7543

JOURNAL ARTICLE

Saha V, Young BD, Freemont PS, 1998, Translocations, fusion genes, and acute leukemia., J Cell Biochem Suppl, Vol: 30-31, Pages: 264-276, ISSN: 0733-1959

Genes involved in chromosomal translocations, associated with the formation of fusion proteins in leukemia, are modular in nature and regulatory in function. It is likely that they are involved in the initiation and maintenance of normal hematopoiesis. A conceptual model is proposed by which disruption of these different genes leads to the development of acute leukemia. Central to this model is the functional interaction between the mammalian trithorax and polycomb group protein complexes. Many of the genes identified in leukemia-associated translocations are likely upstream regulators, co-participators or downstream targets of these complexes. In the natural state, these proteins interact with each other to form multimeric higher-order structures, which sequentially regulate the development of the normal hematopoietic state, either through HOX gene expression or other less defined pathways. The novel interaction domains acquired by the chimaeric fusion products subvert normal cellular control mechanisms, which result in both a failure of cell maturation and activation of anti-apoptotic pathways. The mechanisms by which these translocation products are able to affect these processes are thought to lie at the level of chromatin-mediated transcriptional activation and/or repression. The stimuli for proliferation and development of clinically overt disease may require subsequent mutations in more than one oncogene or tumor suppressor gene, or both. A more comprehensive catalogue of mutation events in malignant cells is therefore required to understand the key regulatory networks that serve to maintain multipotentiality and in particular the modifications which initiate and coordinate commitment in differentiating hematopoietic cells. We propose a model in which common pathways for leukemogenesis lie along the cell cycle control of chromatin structure in terms of transcriptional activation or repression. A clearer understanding of this cascade will provide opportunities

JOURNAL ARTICLE

Grimwade D, Gorman P, Duprez E, Howe K, Langabeer S, Oliver F, Walker H, Culligan D, Waters J, Pomfret M, Goldstone A, Burnett A, Freemont P, Sheer D, Solomon Eet al., 1997, Characterization of cryptic rearrangements and variant translocations in acute promyelocytic leukemia, BLOOD, Vol: 90, Pages: 4876-4885, ISSN: 0006-4971

JOURNAL ARTICLE

Gorman MA, Morera S, Rothwell DG, delaFortelle E, Mol CD, Tainer JA, Hickson ID, Freemont PSet al., 1997, The crystal structure of the human DNA repair endonuclease HAP1 suggests the recognition of extra-helical deoxyribose at DNA abasic sites, EMBO JOURNAL, Vol: 16, Pages: 6548-6558, ISSN: 0261-4189

JOURNAL ARTICLE

Dokurno P, Lally JM, Bates PA, TaylorPapadimitriou J, Band HA, Snary D, Freemont PSet al., 1997, Crystallization of an antitumour antibody SM3 complexed with a peptide epitope, ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, Vol: 53, Pages: 780-781, ISSN: 0907-4449

JOURNAL ARTICLE

Boddy MN, Duprez E, Borden KLB, Freemont PSet al., 1997, Surface residue mutations of the PML RING finger domain alter the formation of nuclear matrix-associated PML bodies, JOURNAL OF CELL SCIENCE, Vol: 110, Pages: 2197-2205, ISSN: 0021-9533

JOURNAL ARTICLE

Kondo H, Rabouille C, Newman R, Levine TP, Pappin D, Freemont P, Warren Get al., 1997, p47 is a cofactor for p97-mediated membrane fusion, NATURE, Vol: 388, Pages: 75-78, ISSN: 0028-0836

JOURNAL ARTICLE

Dokurno P, Lally JM, Bates PA, Band HA, Snary D, Freemont PSet al., 1997, Crystallization of the Fab fragment of the tumour-specific antibody PR1A3, ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, Vol: 53, Pages: 472-473, ISSN: 0907-4449

JOURNAL ARTICLE

Cao TY, Borden KLB, Freemont PS, Etkin LDet al., 1997, Involvement of the rfp tripartite motif in protein-protein interactions and subcellular distribution, JOURNAL OF CELL SCIENCE, Vol: 110, Pages: 1563-1571, ISSN: 0021-9533

JOURNAL ARTICLE

Satijn DPE, Gunster MJ, vanderVlag J, Hamer KM, Schul W, Alkema MJ, Saurin AJ, Freemont PS, vanDriel R, Otte APet al., 1997, RING1 is associated with the polycomb group protein complex and acts as a transcriptional repressor, MOLECULAR AND CELLULAR BIOLOGY, Vol: 17, Pages: 4105-4113, ISSN: 0270-7306

JOURNAL ARTICLE

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