Imperial College London
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ProfessorPaulFreemont

Faculty of Medicine, Department 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

325 results found

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

Howe K, Williamson J, Boddy N, Sheer D, Freemont P, Solomon Eet al., 1998, The ubiquitin-homology gene <i>PIC1</i>:: Characterization of mouse (<i>Pic1</i>) and human (<i>UBL1</i>) 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

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

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-STRUCTURAL BIOLOGY, Vol: 53, Pages: 780-781, ISSN: 2059-7983

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

Newman RH, Freemont PS, 1997, Electron microscopy of thin protein crystals from vapour diffusion 'hanging drops' provides structural information at intermediate resolution, NATO Advanced Study Institute on Electron Crystallography, Publisher: SPRINGER, Pages: 405-406, ISSN: 0168-132X

Conference paper

Rothwell DG, Barzilay G, Gorman M, Morera S, Freemont P, Hickson IDet al., 1997, The structure and functions of the HAP1/Ref-1 protein, ONCOLOGY RESEARCH, Vol: 9, Pages: 275-280, ISSN: 0965-0407

Journal article

Vrielink A, Freemont PS, 1996, Chapter 5 Protein-nucleic acid recognition and interactions, Principles of Medical Biology, Vol: 5, Pages: 85-115, ISSN: 1569-2582

The application of protein crystallography and two-dimensional NMR to study proteins which interact with DNA has provided detailed information about protein-DNA recognition and specificity. Numerous structural motifs have evolved to allow a diverse variety of interactions between proteins and DNA. These include motifs such as the helix-turn-helix, zinc finger, basic region leucine zipper, and ribbon-helix-helix, some of which are found in both prokaryotes and eukaryotes. DNA recognition is usually achieved through specific protein amino acid-DNA base pair interactions which can be mediated via water molecules, in either the major or minor grooves of the DNA. However, interactions between protein side chains and the phosphodiester backbone is a common feature of non-sequence-specific protein-DNA recognition. The flexibility and existence of DNA in a number of different conformations contributes significantly to the overall process of protein-DNA recognition. The enormous variety of protein structures and motifs which can interact with DNA probably reflects the diversity of biological function which requires the formation of protein-DNA complexes. © 1996 Elsevier B.V. All rights reserved.

Journal article

Saurin A, Borden K, Boddy M, Freemont Pet al., 1996, Does this have a familiar RING? (vol 21, pg 208, 1996), TRENDS IN BIOCHEMICAL SCIENCES, Vol: 21, Pages: 453-453, ISSN: 0968-0004

Journal article

Newman RH, Freemont PS, 1996, Use of planar lipid monolayers for 2D crystallisation of proteins and simple analysis of specific lipid-peptide interactions, 7th International Conference on Organized Molecular Films (LB7), Publisher: ELSEVIER SCIENCE SA LAUSANNE, Pages: 18-23, ISSN: 0040-6090

Conference paper

Boddy MN, Howe K, Etkin LD, Solomon E, Freemont PSet al., 1996, PIC 1, a novel ubiquitin-like protein which interacts with the PML component of a multiprotein complex that is disrupted in acute promyelocytic leukaemia, ONCOGENE, Vol: 13, Pages: 971-982, ISSN: 0950-9232

Journal article

Borden KLB, Freemont PS, 1996, The RING finger domain: A recent example of a sequence-structure family, CURRENT OPINION IN STRUCTURAL BIOLOGY, Vol: 6, Pages: 395-401, ISSN: 0959-440X

Journal article

Saurin AJ, Borden KLB, Boddy MN, Freemont PSet al., 1996, Does this have a familiar RING?, TRENDS IN BIOCHEMICAL SCIENCES, Vol: 21, Pages: 208-214, ISSN: 0968-0004

Journal article

Newman RH, Whitehead P, Lally J, Coffer A, Freemont Pet al., 1996, 20S human proteasomes bind with a specific orientation to lipid monolayers in vitro, BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, Vol: 1281, Pages: 111-116, ISSN: 0005-2736

Journal article

Borden KLB, Lally JM, Martin SR, OReilly NJ, Solomon E, Freemont PSet al., 1996, In vivo and in vitro characterization of the B1 and B2 zinc-binding domains from the acute promyelocytic leukemia protooncoprotein PML, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 93, Pages: 1601-1606, ISSN: 0027-8424

Journal article

Otto WR, Rao JD, Cox HM, Kotzian E, Lee CY, Goodlad RA, Lane A, Gorman M, Freemont PA, Hansen HF, Pappin D, Wright NAet al., 1996, Effects of pancreatic spasmolytic polypeptide (PSP) on epithelial cell function, EUROPEAN JOURNAL OF BIOCHEMISTRY, Vol: 235, Pages: 64-72, ISSN: 0014-2956

Journal article

Brown DG, Freemont PS, 1996, Crystallography in the study of protein-DNA interactions., Methods Mol Biol, Vol: 56, Pages: 293-318, ISSN: 1064-3745

Journal article

BORDEN KLB, LALLY JM, MARTIN SR, OREILLY NJ, ETKIN LD, FREEMONT PSet al., 1995, NOVEL TOPOLOGY OF A ZINC-BINDING DOMAIN FROM A PROTEIN INVOLVED IN REGULATING EARLY XENOPUS DEVELOPMENT, EMBO JOURNAL, Vol: 14, Pages: 5947-5956, ISSN: 0261-4189

Journal article

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