Imperial College London

ProfessorPaulFreemont

Faculty of MedicineDepartment of Infectious Disease

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

255 results found

Rothwell DG, Hang B, Gorman MA, Freemont PS, Singer B, Hickson IDet al., 2000, Substitution of Asp-210 in HAP1 (APE/Ref-1) eliminates endonuclease activity but stabilises substrate binding, NUCLEIC ACIDS RESEARCH, Vol: 28, Pages: 2207-2213, ISSN: 0305-1048

Journal article

Zhong S, Muller S, Ronchetti S, Freemont PS, Dejean A, Pandolfi PPet al., 2000, Role of SUMO-1-modified PML in nuclear body formation, BLOOD, Vol: 95, Pages: 2748-2753, ISSN: 0006-4971

Journal article

Freemont PS, 2000, RING for destruction?, Curr Biol, Vol: 10, Pages: R84-R87, ISSN: 0960-9822

Ubiquitination targets proteins for degradation and is a potent regulator of cellular protein function. Recent results implicate the RING finger domain in specific ubiquitination events; it is possible that all RING proteins act as E3 ubiquitin protein ligases, with implications for a variety of biological areas.

Journal article

Freemont PS, 2000, Ubiquitination: RING for destruction?, CURRENT BIOLOGY, Vol: 10, Pages: R84-R87, ISSN: 0960-9822

Journal article

Lariviere L, Rueger W, Freemont P, Morera Set al., 2000, beta-Glucosyltranferase: Substrate Binding and metal site., Publisher: INT UNION CRYSTALLOGRAPHY, Pages: S242-S242, ISSN: 2053-2733

Conference paper

Zhong S, Muller S, Ronchetti S, Freemont P, Dejean A, Pandolfi PPet al., 1999, PML is essential for proper formation of the nuclear body., BLOOD, Vol: 94, Pages: 489A-489A, ISSN: 0006-4971

Journal article

Muller JMM, Rabouille C, Newman R, Shorter J, Freemont P, Schiavo G, Warren G, Shima DTet al., 1999, An NSF function distinct from ATPase-dependent SNARE disassembly is essential for Golgi membrane fusion, NATURE CELL BIOLOGY, Vol: 1, Pages: 335-340, ISSN: 1465-7392

Journal article

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

Lally JM, Dokurno P, Taylor-Papadimitriou J, Freemont PSet al., 1999, CRYSTAL STRUCTURE OF THE SM3 ANTIBODY AGAINST POLYMORPHIC EPITHELIAL MUCIN, Publisher: INT UNION CRYSTALLOGRAPHY, Pages: 351-351, ISSN: 2053-2733

Conference paper

Zhang X, Morera S, Bates PA, Whitehead PC, Coffer AI, Hainbucher K, Nash RA, Sternberg MJE, Lindahl T, Freemont PSet al., 1999, STRUCTURE OF AN XRCC1 BRCT DOMAIN: A NEW PROTEIN PROTEIN INTERACTION MODULE., Publisher: INT UNION CRYSTALLOGRAPHY, Pages: 292-292, ISSN: 2053-2733

Conference paper

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

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

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

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

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

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

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