Paul R Clarke

Summary

Affiliation: University of Dundee
Country: UK

Publications

  1. ncbi request reprint A mitotic role for BRCA1/BARD1 in tumor suppression?
    Paul R Clarke
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
    Cell 127:453-5. 2006
  2. ncbi request reprint Mitosis: ran scales the alps of spindle formation
    Paul R Clarke
    Biomedical Research Centre, Level 5, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
    Curr Biol 17:R643-5. 2007
  3. doi request reprint Signaling to nuclear transport
    Paul R Clarke
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
    Dev Cell 14:316-8. 2008
  4. doi request reprint Cell-cycle control in the face of damage--a matter of life or death
    Paul R Clarke
    Biomedical Research Institute, College of Medicine, Dentistry and Nursing, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK
    Trends Cell Biol 19:89-98. 2009
  5. doi request reprint Spatial and temporal coordination of mitosis by Ran GTPase
    Paul R Clarke
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK
    Nat Rev Mol Cell Biol 9:464-77. 2008
  6. ncbi request reprint Cleavage of claspin by caspase-7 during apoptosis inhibits the Chk1 pathway
    Catriona A L Clarke
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
    J Biol Chem 280:35337-45. 2005
  7. pmc The methylated N-terminal tail of RCC1 is required for stabilisation of its interaction with chromatin by Ran in live cells
    Ekarat Hitakomate
    Biomedical Research Institute, School of Medicine, College of Medicine, Dentistry and Nursing, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
    BMC Cell Biol 11:43. 2010
  8. doi request reprint Claspin is phosphorylated in the Chk1-binding domain by a kinase distinct from Chk1
    Lara N Bennett
    Biomedical Research Centre, Level 5, College of Medicine Dentistry and Nursing, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK
    Biochem Biophys Res Commun 369:973-6. 2008
  9. pmc Phosphorylation of Mcl-1 by CDK1-cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest
    Margaret E Harley
    Biomedical Research Institute, School of Medicine, College of Medicine, Dentistry and Nursing, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, UK
    EMBO J 29:2407-20. 2010
  10. ncbi request reprint Many fingers on the mitotic trigger: post-translational regulation of the Cdc25C phosphatase
    James R A Hutchins
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee Scotland, UK
    Cell Cycle 3:41-5. 2004

Collaborators

Detail Information

Publications39

  1. ncbi request reprint A mitotic role for BRCA1/BARD1 in tumor suppression?
    Paul R Clarke
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
    Cell 127:453-5. 2006
    ..In this issue of Cell, Joukov et al. demonstrate that the BRCA1/BARD1 heterodimer participates in mitotic spindle assembly, a process conducted by the GTPase Ran. Loss of this mitotic function might contribute to tumorigenesis...
  2. ncbi request reprint Mitosis: ran scales the alps of spindle formation
    Paul R Clarke
    Biomedical Research Centre, Level 5, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
    Curr Biol 17:R643-5. 2007
    ..Alp7/TACC has been identified as an important target for Ran GTPase in spindle formation in fission yeast. This discovery underlines a general role for Ran in orchestrating mitosis in all eukaryotes...
  3. doi request reprint Signaling to nuclear transport
    Paul R Clarke
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
    Dev Cell 14:316-8. 2008
    ..This mechanism may coordinate nucleocytoplasmic transport with other mitogenic effects of these pathways...
  4. doi request reprint Cell-cycle control in the face of damage--a matter of life or death
    Paul R Clarke
    Biomedical Research Institute, College of Medicine, Dentistry and Nursing, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK
    Trends Cell Biol 19:89-98. 2009
    ..These findings shed new light on how the balance between cell-cycle progression and cell death is controlled...
  5. doi request reprint Spatial and temporal coordination of mitosis by Ran GTPase
    Paul R Clarke
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK
    Nat Rev Mol Cell Biol 9:464-77. 2008
    ..The mechanisms that underlie these functions provide insights into the spatial and temporal coordination of the changes that occur in intracellular organization during the cell-division cycle...
  6. ncbi request reprint Cleavage of claspin by caspase-7 during apoptosis inhibits the Chk1 pathway
    Catriona A L Clarke
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
    J Biol Chem 280:35337-45. 2005
    ..These results indicate that cleavage of Claspin by caspase-7 inactivates the Chk1 signaling pathway. This mechanism may regulate the balance between cell cycle arrest and induction of apoptosis during the response to genotoxic stress...
  7. pmc The methylated N-terminal tail of RCC1 is required for stabilisation of its interaction with chromatin by Ran in live cells
    Ekarat Hitakomate
    Biomedical Research Institute, School of Medicine, College of Medicine, Dentistry and Nursing, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
    BMC Cell Biol 11:43. 2010
    ..In vitro, the association of Ran with RCC1 induces a conformational change in the N-terminal tail that promotes its interaction with DNA...
  8. doi request reprint Claspin is phosphorylated in the Chk1-binding domain by a kinase distinct from Chk1
    Lara N Bennett
    Biomedical Research Centre, Level 5, College of Medicine Dentistry and Nursing, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK
    Biochem Biophys Res Commun 369:973-6. 2008
    ..These results demonstrate that phosphorylation of Claspin within the Chk1-binding domain is catalysed by an ATR-dependent kinase distinct from Chk1...
  9. pmc Phosphorylation of Mcl-1 by CDK1-cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest
    Margaret E Harley
    Biomedical Research Institute, School of Medicine, College of Medicine, Dentistry and Nursing, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, UK
    EMBO J 29:2407-20. 2010
    ..Regulation of apoptosis, therefore, is linked intrinsically to progression through mitosis and is governed by a temporal mechanism that distinguishes between normal mitosis and prolonged mitotic arrest...
  10. ncbi request reprint Many fingers on the mitotic trigger: post-translational regulation of the Cdc25C phosphatase
    James R A Hutchins
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee Scotland, UK
    Cell Cycle 3:41-5. 2004
    ..Thus, the regulation of Cdc25C activity and localization integrates multiple signals that govern the decision to enter mitosis...
  11. ncbi request reprint Regulation of Claspin degradation by the ubiquitin-proteosome pathway during the cell cycle and in response to ATR-dependent checkpoint activation
    Lara N Bennett
    Biomedical Research Centre, Level 5, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK
    FEBS Lett 580:4176-81. 2006
    ..Thus, the Chk1 pathway is regulated through both phosphorylation of Claspin and its controlled degradation...
  12. doi request reprint DYRK1A phosphorylates caspase 9 at an inhibitory site and is potently inhibited in human cells by harmine
    Anne Seifert
    Biomedical Research Institute, College of Medicine, Dentistry and Nursing, University of Dundee, UK
    FEBS J 275:6268-80. 2008
    ..Regulation of apoptosis through inhibitory phosphorylation of caspase 9 may play a role in the function of DYRK1A during development and in pathogenesis...
  13. ncbi request reprint RCC1 isoforms differ in their affinity for chromatin, molecular interactions and regulation by phosphorylation
    Fiona E Hood
    Biomedical Research Centre, Level 5, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK
    J Cell Sci 120:3436-45. 2007
    ..These results show that human RCC1 isoforms have distinct chromatin binding properties, different molecular interactions, and are selectively regulated by phosphorylation, as determined by their different NTRs...
  14. ncbi request reprint Phosphorylation regulates the dynamic interaction of RCC1 with chromosomes during mitosis
    James R A Hutchins
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, United Kingdom
    Curr Biol 14:1099-104. 2004
    ..This mechanism may be important for the localized generation of Ran-GTP on chromatin after nuclear envelope breakdown and may play a role in the coordination of progression through mitosis...
  15. pmc Regulation of Cdc2/cyclin B activation in Xenopus egg extracts via inhibitory phosphorylation of Cdc25C phosphatase by Ca(2+)/calmodulin-dependent protein [corrected] kinase II
    James R A Hutchins
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
    Mol Biol Cell 14:4003-14. 2003
    ..CaMKII delays Cdc2/cyclin B activation via phosphorylation of Cdc25C at S287 in egg extracts, indicating that this pathway regulates the timing of mitosis during the early embryonic cell cycle...
  16. pmc Dynamic localisation of Ran GTPase during the cell cycle
    James R A Hutchins
    Biomedical Research Institute, College of Medicine, Dentistry and Nursing, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
    BMC Cell Biol 10:66. 2009
    ..The activity of Ran is determined by both its guanine nucleotide-bound state and its subcellular localization...
  17. doi request reprint Microtubule assembly by the Apc protein is regulated by importin-beta--RanGTP
    Dina Dikovskaya
    Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    J Cell Sci 123:736-46. 2010
    ..Thus, importin-beta binds to Apc and negatively regulates the MT-assembly and spindle-promoting activity of Apc in a Ran-regulatable manner...
  18. ncbi request reprint The docking interaction of caspase-9 with ERK2 provides a mechanism for the selective inhibitory phosphorylation of caspase-9 at threonine 125
    Morag C Martin
    Biomedical Research Centre, Ninewells Hospital and Medical School, Level 5, University of Dundee, Dundee DD1 9SY, United Kingdom
    J Biol Chem 283:3854-65. 2008
    ..This selectivity may be important for the antiapoptotic role of classical MAPKs in contrast to the proapoptotic roles of stress-activated MAPKs...
  19. ncbi request reprint Phosphorylation of caspase-9 by CDK1/cyclin B1 protects mitotic cells against apoptosis
    Lindsey A Allan
    Biomedical Research Centre, Level 5, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK
    Mol Cell 26:301-10. 2007
    ..Thus, phosphorylation of caspase-9 at Thr125 sets the threshold for activation of the intrinsic apoptotic pathway during the cell cycle, restrains apoptosis during mitosis, and determines sensitivity to antimitotic drugs...
  20. ncbi request reprint Cell biology. A gradient signal orchestrates the mitotic spindle
    Paul R Clarke
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
    Science 309:1334-5. 2005
  21. ncbi request reprint Protein kinase A regulates caspase-9 activation by Apaf-1 downstream of cytochrome c
    Morag C Martin
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Scotland, United Kingdom
    J Biol Chem 280:15449-55. 2005
    ..These data indicate that extracellular signals that elevate cyclic AMP and activate protein kinase A may suppress apoptosis by inhibiting apoptosome formation downstream of cytochrome c release from mitochondria...
  22. doi request reprint hnRNP-U is a specific DNA-dependent protein kinase substrate phosphorylated in response to DNA double-strand breaks
    Fredrik M Berglund
    Biomedical Research Institute, College of Medicine, Dentistry and Nursing, University of Dundee, Level 5, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK
    Biochem Biophys Res Commun 381:59-64. 2009
    ..We show that hnRNP-U is phosphorylated at Ser59 by DNA-PK in vitro and in cells in response to DNA double-strand breaks. Phosphorylation of hnRNP-U suggests novel functions for DNA-PK in the response to DNA damage...
  23. pmc Regulation of caspase 9 through phosphorylation by protein kinase C zeta in response to hyperosmotic stress
    Suzanne C Brady
    Biomedical Research Centre, Level 5, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
    Mol Cell Biol 25:10543-55. 2005
    ..This work provides further evidence that caspase 9 acts as a focal point for multiple protein kinase signaling pathways that regulate apoptosis...
  24. ncbi request reprint Cell biology: Ran, mitosis and the cancer connection
    Helen S Sanderson
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
    Curr Biol 16:R466-8. 2006
    ..The small GTPase Ran has been shown to regulate HURP, a protein that interacts with several mitotic spindle assembly factors. This discovery sheds new light on the role of Ran in the fidelity of mitosis and in cancer...
  25. ncbi request reprint Concentration of Ran on chromatin induces decondensation, nuclear envelope formation and nuclear pore complex assembly
    Chuanmao Zhang
    Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, UK
    Eur J Cell Biol 81:623-33. 2002
    ..We propose that the biological activity of Ran is determined by its targeting to structures such as chromatin as well as its guanine nucleotide bound state...
  26. ncbi request reprint Targeting of RCC1 to chromosomes is required for proper mitotic spindle assembly in human cells
    William Moore
    Biomedical Research Centre, University of Dundee, Level 5, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, United Kingdom
    Curr Biol 12:1442-7. 2002
    ..Defects in this system may result in abnormal chromosome segregation and genomic instability, which are characteristic of many cancer cells...
  27. ncbi request reprint Dephosphorylation of the inhibitory phosphorylation site S287 in Xenopus Cdc25C by protein phosphatase-2A is inhibited by 14-3-3 binding
    James R A Hutchins
    Biomedical Research Centre, Level 5, Ninewells Hospital and Medical School, University of Dundee, UK
    FEBS Lett 528:267-71. 2002
    ..The rate of dephosphorylation of S287 is not increased in mitotic extracts, indicating that the phosphorylation status of the site is likely to be controlled through modulation of kinases or 14-3-3 binding activity...
  28. doi request reprint Apoptosis and autophagy: Regulation of caspase-9 by phosphorylation
    Lindsey A Allan
    Biomedical Research Institute, School of Medicine, College of Medicine, Dentistry and Nursing, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, UK
    FEBS J 276:6063-73. 2009
    ..Here, we review these advances and discuss the possible roles of caspase-9 phosphorylation in the regulation of apoptosis during development and in pathological states, including cancer...
  29. ncbi request reprint A mechanism coupling cell division and the control of apoptosis
    Lindsey A Allan
    Biomedical Research Centre, University of Dundee, UK
    SEB Exp Biol Ser 59:257-65. 2008
    ..This mechanism may play an important role in anti-cancer surveillance and might be exploited to improve cell killing by anti-cancer drugs that target mitotic cells...
  30. ncbi request reprint Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK
    Lindsey A Allan
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
    Nat Cell Biol 5:647-54. 2003
    ..This mechanism may also contribute to tumorigenesis when the ERK MAPK pathway is constitutively activated...
  31. pmc DNA-dependent phosphorylation of Chk1 and Claspin in a human cell-free system
    Catriona A L Clarke
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
    Biochem J 388:705-12. 2005
    ..This cell-free system will facilitate further biochemical analysis of the Chk1 pathway in humans...
  32. doi request reprint p38alpha- and DYRK1A-dependent phosphorylation of caspase-9 at an inhibitory site in response to hyperosmotic stress
    Anne Seifert
    Biomedical Research Institute, School of Medicine, College of Medicine, Dentistry and Nursing, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK
    Cell Signal 21:1626-33. 2009
    ..Phosphorylation of caspase-9 at Thr125 may restrain apoptosis during the acute response to hyperosmotic stress...
  33. ncbi request reprint Role of importin-beta in the control of nuclear envelope assembly by Ran
    Chuanmao Zhang
    Biomedical Research Centre, Level 5, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom
    Curr Biol 12:498-502. 2002
    ..Importin-beta links NE assembly, mitotic spindle assembly, and nucleocytoplasmic transport to regulation by Ran and may coordinate these processes during cell division...
  34. pmc To the centre of the volcano. Workshop on the mechanisms of nucleocytoplasmic transport
    Maarten Fornerod
    Department of Tumor Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands
    EMBO Rep 9:419-24. 2008
  35. doi request reprint Cyclin B1 is localized to unattached kinetochores and contributes to efficient microtubule attachment and proper chromosome alignment during mitosis
    Qiang Chen
    The MOE Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Bio membrane and Membrane Bio engineering, College of Life Sciences, Peking University, Beijing 100871, China
    Cell Res 18:268-80. 2008
    ..Cyclin B1 is then transported from each kinetochore as microtubule attachment is completed, and this relocalization may redirect the activity of cyclin B1-CDK1 and contribute to inactivation of the spindle assembly checkpoint...
  36. ncbi request reprint The Crm de la crème of mitosis
    Paul R Clarke
    Nat Cell Biol 7:551-2. 2005
  37. ncbi request reprint Anchoring RCC1 by the tail
    Paul R Clarke
    Nat Cell Biol 9:485-7. 2007
  38. ncbi request reprint The importin-beta P446L dominant-negative mutant protein loses RanGTP binding ability and blocks the formation of intact nuclear envelope
    Gyula Timinszky
    The University of Szeged, Faculty of Medicine, Department of Biology, Somogyi B u 4, H 6720 Szeged, Hungary
    J Cell Sci 115:1675-87. 2002
    ..However, it interferes with nuclear envelope formation during mitosis-to-interphase transition, revealing a novel function of importin-beta...
  39. ncbi request reprint Nuclear pores: sowing the seeds of assembly on the chromatin landscape
    Richard Wozniak
    Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada T6R 2A4
    Curr Biol 13:R970-2. 2003