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Greenfield Sluder PhD

TitleProfessor Emeritus
InstitutionUniversity of Massachusetts Medical School
DepartmentRadiology
AddressUniversity of Massachusetts Medical School
377 Plantation Street
Worcester MA 01605
Phone508-856-8651
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    Other Positions
    InstitutionUMMS - School of Medicine
    DepartmentRadiology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentCell Biology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentInterdisciplinary Graduate Program


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    Collapse Biography 
    Collapse education and training
    Middlebury College, Middlebury, VT, United StatesABLiberal Arts
    University of Pennsylvania, Philadelphia, PA, United StatesPH DPhilosophy

    Collapse Overview 
    Collapse overview

    Academic Background

    Kip Sluder received his A.B. from Middlebury College in 1968 andhis Ph.D. from the University of Pennsylvania in 1976. After an AmericanCancer Society post-doctoral fellowship with Dan Mazia at the Universityof California, Berkeley (1977 to 1980), he joined the faculty of the WorcesterFoundation for Experimental Biology in 1981. Since 1990, he has servedas co-director of the Analytical and Quantitative Light Microscopy Courseat the Marine Biological Laboratory, in Woods Hole Massachusetts.In 1997 Kip joined the Cell Biology Department at the University of MassachusettsMedical School as a Professor.

    Mitosis

    Our research is centered on the mechanisms that control various aspects of cell division. Applying microscopic and biophysical methods, we seek to elucidate the functional properties of control mechanisms as they operate in the living cell. Our results establish the basis for the integration of cell function with advances in the molecular biology of regulatory pathways. We use echinoderm zygotes, frog egg extracts, and cultured cells as model systems.

    One of the major projects in the laboratory seeks to elucidate the controls that ensure that the interphase centrosome reproduces, or doubles, only once in each cell cycle in proper coordination with nuclear events. We have recently shown that centrosome reproduction is coordinated with nuclear events by activities that function during S phase of the cell cycle.

    We have also developed the first Xenopus egg extract system that supports repeated rounds of centrosome reproduction in vitro. Using this system we have shown that the activity of the cyclin dependent kinase 2- cyclin E complex (Cdk2-cyclin E) is required for multiple rounds of centrosome duplication.

    Figures

    Uetake and Sluder Figure 2

    Figure 1: Mammalian cells. (A and B) Overlaid phase and fluorescence images showing BrdU incorporation in mononucleate and binucleate cells. (A) Cells were previously treated with 0.5 µM cytochalasin D and cultured on bare glass. Mononucleate cells have incorporated BrdU, whereas the binucleates have not. (B) Cells treated with 0.5 µM cytochalasin D and cultured on fibronectin-coated glass. Both the mononucleate and binucleate cells have incorporated BrdU. (C) Cells previously treated with 0.5 µM cytochalasin D and cultured on fibronectin-coated glass (images taken from Video 4, available at http://www.jcb.org/cgi/content/full/jcb.200403014/DC1). Frames from a video sequence of two binucleate cells in the same field progressing through mitosis. The first to enter mitosis (top row) divides into two, whereas the second (bottom row) divides into three. Phase-contrast microscopy. Times are in h:min after cytochalasin D removal. Bars, 50 µm.

    Figure 1

    Figure 2: Repeated rounds of centrosome duplication in an aphidicolin-treated Xenopus egg extract. Frames from a time-lapse video sequence, showing the increase in aster number over time in a microscope field. The decrease in aster number in panel d is due to the migration of asters from the plane of focus and field of view. Minutes after addition of sperm nuclei are seen in the lower right corner of each frame. Polarization optics. 10 microns per scale division.

    In other studies we have characterized the cell cycle checkpoint controls for the metaphase-anaphase transition. These checkpoint pathways serve to ensure the equal distribution of chromosomes during cell division. We have demonstrated that signal transducing molecules in the kinetochore monitor chromosome attachment to the spindle and that even one unattached kinetochore will block the metaphase-anaphase transition.

    Using GFP-cyclin B and confocal microscopy we are also investigating how the checkpoint pathway that monitors the completion of DNA synthesis controls nuclear envelope breakdown and entry of the cell into mitosis.



    Collapse Rotation Projects

    Potential Rotation Projects

    We favor having students work independently on defined projects that have promise of completion during the study period.

    Project #1: Use a frog egg extract that supports multiple rounds of centrosome duplication in vitro to investigate the role of various high interest kinases in the control of centrosome duplication. Also, we can use these extracts to further investigate how various other proteins interact with the centrosome to influence its duplication.

    Hinchcliffe, E.H., C. Li, E.A. Thompson, J.L. Maller and G. Sluder. 1999. Requirement of Cdk2-cyclin E activity for repeated centrosome reproduction in Xenopus egg extract. Science 283:851-854.

    Project #2: Use microsurgery and immunofluorescence on BSC-1 cells to further investigate how centrioles influence the interphase progression of the cell cycle.

    Hinchcliffe, E.H., F.J. Miller, M. Cham, A. Khodjakov and G. Sluder. 2001. Requirement of a centrosomal activity for cell cycle progression through G1 into S phase. Science 291: 1547-1550.



    Collapse Post Docs

    A postdoctoral position is available to study in this laboratory. Contact Dr. Sluder for additional details.


    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Uetake Y, Sluder G. Activation of the apoptotic pathway during prolonged prometaphase blocks daughter cell proliferation. Mol Biol Cell. 2018 Aug 22; mbcE18010026. PMID: 30133342.
      View in: PubMed
    2. Duronio RJ, O'Farrell PH, Sluder G, Su TT. Sophisticated lessons from simple organisms: appreciating the value of curiosity-driven research. Dis Model Mech. 2017 Dec 19; 10(12):1381-1389. PMID: 29259023.
      View in: PubMed
    3. Matijasevic Z, Krzywicka-Racka A, Sluder G, Gallant J, Jones SN. The Zn-finger domain of MdmX suppresses cancer progression by promoting genome stability in p53-mutant cells. Oncogenesis. 2016 Oct 03; 5(10):e262. PMID: 27694836.
      View in: PubMed
    4. Douthwright S, Sluder G. Live cell imaging: Assessing the phototoxicity of 488 nm and 546 nm light and methods to alleviate it. J Cell Physiol. 2016 Sep 08. PMID: 27608139.
      View in: PubMed
    5. Sluder G. Using sea urchin gametes and zygotes to investigate centrosome duplication. Cilia. 2016; 5(1):20. PMID: 27602205.
      View in: PubMed
    6. Lambrus BG, Daggubati V, Uetake Y, Scott PM, Clutario KM, Sluder G, Holland AJ. A USP28-53BP1-p53-p21 signaling axis arrests growth after centrosome loss or prolonged mitosis. J Cell Biol. 2016 Jul 18; 214(2):143-53. PMID: 27432896.
      View in: PubMed
    7. Wu Q, Madany P, Akech J, Dobson JR, Douthwright S, Browne G, Colby JL, Winter GE, Bradner JE, Pratap J, Sluder G, Bhargava R, Chiosea SI, van Wijnen AJ, Stein JL, Stein GS, Lian JB, Nickerson JA, Imbalzano AN. The SWI/SNF ATPases Are Required for Triple Negative Breast Cancer Cell Proliferation. J Cell Physiol. 2015 Nov; 230(11):2683-94. PMID: 25808524.
      View in: PubMed
    8. Lambrus BG, Uetake Y, Clutario KM, Daggubati V, Snyder M, Sluder G, Holland AJ. p53 protects against genome instability following centriole duplication failure. J Cell Biol. 2015 Jul 6; 210(1):63-77. PMID: 26150389.
      View in: PubMed
    9. Douthwright S, Sluder G. Link between DNA damage and centriole disengagement/reduplication in untransformed human cells. J Cell Physiol. 2014 Oct; 229(10):1427-36. PMID: 24532022.
      View in: PubMed
    10. Sluder G. One to only two: a short history of the centrosome and its duplication. Philos Trans R Soc Lond B Biol Sci. 2014 Sep 5; 369(1650). PMID: 25047609.
      View in: PubMed
    11. Sluder G. Centriole engagement: it's not just cohesin any more. Curr Biol. 2013 Aug 5; 23(15):R659-60. PMID: 23928085.
      View in: PubMed
    12. Sluder G, Wolf DE. Preface. Digital microscopy. Methods Cell Biol. 2013; 114:xix-xx. PMID: 23931526.
      View in: PubMed
    13. Nordberg JJ, Sluder G. Practical aspects of adjusting digital cameras. Methods Cell Biol. 2013; 114:151-62. PMID: 23931506.
      View in: PubMed
    14. Sluder G, Nordberg JJ. Microscope basics. Methods Cell Biol. 2013; 114:1-10. PMID: 23931500.
      View in: PubMed
    15. Hatano T, Sluder G. The interrelationship between APC/C and Plk1 activities in centriole disengagement. Biol Open. 2012 Nov 15; 1(11):1153-60. PMID: 23213396.
      View in: PubMed
    16. Krzywicka-Racka A, Sluder G. Repeated cleavage failure does not establish centrosome amplification in untransformed human cells. J Cell Biol. 2011 Jul 25; 194(2):199-207. PMID: 21788368.
      View in: PubMed
    17. Sluder G, Khodjakov A. Centriole duplication: analogue control in a digital age. Cell Biol Int. 2010 Dec; 34(12):1239-45. PMID: 21067522.
      View in: PubMed
    18. Uetake Y, Sluder G. Prolonged prometaphase blocks daughter cell proliferation despite normal completion of mitosis. Curr Biol. 2010 Sep 28; 20(18):1666-71. PMID: 20832310.
      View in: PubMed
    19. Heilman SA, Nordberg JJ, Liu Y, Sluder G, Chen JJ. Abrogation of the postmitotic checkpoint contributes to polyploidization in human papillomavirus E7-expressing cells. J Virol. 2009 Mar; 83(6):2756-64. PMID: 19129456.
      View in: PubMed
    20. Schnackenberg BJ, Marzluff WF, Sluder G. Cyclin E in centrosome duplication and reduplication in sea urchin zygotes. J Cell Physiol. 2008 Dec; 217(3):626-31. PMID: 18651565.
      View in: PubMed
    21. Matijasevic Z, Krzywicka-Racka A, Sluder G, Jones SN. MdmX regulates transformation and chromosomal stability in p53-deficient cells. Cell Cycle. 2008 Oct; 7(19):2967-73. PMID: 18818521.
      View in: PubMed
    22. Uetake Y, Sluder G. Cell-cycle progression without an intact microtuble cytoskeleton. Curr Biol. 2007 Dec 4; 17(23):2081-6. PMID: 18060787.
      View in: PubMed
    23. Loncarek J, Sluder G, Khodjakov A. Centriole biogenesis: a tale of two pathways. Nat Cell Biol. 2007 Jul; 9(7):736-8. PMID: 17603508.
      View in: PubMed
    24. Liu Y, Heilman SA, Illanes D, Sluder G, Chen JJ. p53-independent abrogation of a postmitotic checkpoint contributes to human papillomavirus E6-induced polyploidy. Cancer Res. 2007 Mar 15; 67(6):2603-10. PMID: 17363579.
      View in: PubMed
    25. Uetake Y, Loncarek J, Nordberg JJ, English CN, La Terra S, Khodjakov A, Sluder G. Cell cycle progression and de novo centriole assembly after centrosomal removal in untransformed human cells. J Cell Biol. 2007 Jan 15; 176(2):173-82. PMID: 17227892.
      View in: PubMed
    26. Sluder G, Nordberg JJ. Microscope basics. Methods Cell Biol. 2007; 81:1-10. PMID: 17519159.
      View in: PubMed
    27. Nordberg JJ, Sluder G. Practical aspects of adjusting digital cameras. Methods Cell Biol. 2007; 81:159-69. PMID: 17519167.
      View in: PubMed
    28. Sluder G, Nordberg JJ, Miller FJ, Hinchcliffe EH. A sealed preparation for long-term observations of cultured cells. CSH Protoc. 2007; 2007:pdb.prot4660. PMID: 21356931.
      View in: PubMed
    29. Sluder G, Nordberg JJ, Miller FJ, Hinchcliffe EH. A sealed preparation for long-term observations of cultured cells: details of support slide construction. CSH Protoc. 2007; 2007:pdb.ip26. PMID: 21356920.
      View in: PubMed
    30. Hinchcliffe EH, Sluder G. Working with classic video. Methods Cell Biol. 2007; 81:141-57. PMID: 17519166.
      View in: PubMed
    31. Sluder G. Two-way traffic: centrosomes and the cell cycle. Nat Rev Mol Cell Biol. 2005 Sep; 6(9):743-8. PMID: 16231423.
      View in: PubMed
    32. Ehrhardt AG, Sluder G. Spindle pole fragmentation due to proteasome inhibition. J Cell Physiol. 2005 Sep; 204(3):808-18. PMID: 15828030.
      View in: PubMed
    33. La Terra S, English CN, Hergert P, McEwen BF, Sluder G, Khodjakov A. The de novo centriole assembly pathway in HeLa cells: cell cycle progression and centriole assembly/maturation. J Cell Biol. 2005 Feb 28; 168(5):713-22. PMID: 15738265.
      View in: PubMed
    34. Murata-Hori M, Sluder G, Wang YL. Regulation of cell cycle by the anaphase spindle midzone. BMC Cell Biol. 2004 Dec 23; 5(1):49. PMID: 15617574.
      View in: PubMed
    35. Uetake Y, Sluder G. Cell cycle progression after cleavage failure: mammalian somatic cells do not possess a "tetraploidy checkpoint". J Cell Biol. 2004 Jun 7; 165(5):609-15. PMID: 15184397.
      View in: PubMed
    36. Sluder G, Nordberg JJ. The good, the bad and the ugly: the practical consequences of centrosome amplification. Curr Opin Cell Biol. 2004 Feb; 16(1):49-54. PMID: 15037304.
      View in: PubMed
    37. Hinchcliffe EH, Sluder G. "Do not (mis-)adjust your set": maintaining specimen detail in the video microscope. Methods Cell Biol. 2003; 72:65-85. PMID: 14719328.
      View in: PubMed
    38. Sluder G, Nordberg JJ. Microscope basics. Methods Cell Biol. 2003; 72:1-10. PMID: 14719324.
      View in: PubMed
    39. Khodjakov A, Rieder CL, Sluder G, Cassels G, Sibon O, Wang CL. De novo formation of centrosomes in vertebrate cells arrested during S phase. J Cell Biol. 2002 Sep 30; 158(7):1171-81. PMID: 12356862.
      View in: PubMed
    40. Hinchcliffe EH, Sluder G. Two for two: Cdk2 and its role in centrosome doubling. Oncogene. 2002 Sep 9; 21(40):6154-60. PMID: 12214244.
      View in: PubMed
    41. Hinchcliffe EH, Sluder G. Centrosome duplication: three kinases come up a winner! Curr Biol. 2001 Sep 4; 11(17):R698-701. PMID: 11553343.
      View in: PubMed
    42. Hinchcliffe EH, Sluder G. "It takes two to tango": understanding how centrosome duplication is regulated throughout the cell cycle. Genes Dev. 2001 May 15; 15(10):1167-81. PMID: 11358861.
      View in: PubMed
    43. Hinchcliffe EH, Miller FJ, Cham M, Khodjakov A, Sluder G. Requirement of a centrosomal activity for cell cycle progression through G1 into S phase. Science. 2001 Feb 23; 291(5508):1547-50. PMID: 11222860.
      View in: PubMed
    44. Hinchcliffe EH, Sluder G. Centrosome reproduction in Xenopus lysates. Methods Cell Biol. 2001; 67:269-87. PMID: 11550474.
      View in: PubMed
    45. Palmieri SJ, Nebl T, Pope RK, Seastone DJ, Lee E, Hinchcliffe EH, Sluder G, Knecht D, Cardelli J, Luna EJ. Mutant Rac1B expression in Dictyostelium: effects on morphology, growth, endocytosis, development, and the actin cytoskeleton. Cell Motil Cytoskeleton. 2000 Aug; 46(4):285-304. PMID: 10962483.
      View in: PubMed
    46. Suprynowicz FA, Groigno L, Whitaker M, Miller FJ, Sluder G, Sturrock J, Whalley T. Activation of protein kinase C alters p34(cdc2) phosphorylation state and kinase activity in early sea urchin embryos by abolishing intracellular Ca2+ transients. Biochem J. 2000 Jul 15; 349(Pt 2):489-99. PMID: 10880348.
      View in: PubMed
    47. Sluder G, McCollum D. Molecular biology. The mad ways of meiosis. Science. 2000 Jul 14; 289(5477):254-5. PMID: 10917849.
      View in: PubMed
    48. Sluder G, Hinchcliffe EH. The coordination of centrosome reproduction with nuclear events during the cell cycle. Curr Top Dev Biol. 2000; 49:267-89. PMID: 11005023.
      View in: PubMed
    49. Sluder G, Hinchcliffe EH. Control of centrosome reproduction: the right number at the right time. Biol Cell. 1999 Jul; 91(6):413-27. PMID: 10519003.
      View in: PubMed
    50. Hinchcliffe EH, Thompson EA, Miller FJ, Yang J, Sluder G. Nucleo-cytoplasmic interactions that control nuclear envelope breakdown and entry into mitosis in the sea urchin zygote. J Cell Sci. 1999 Apr; 112 ( Pt 8):1139-48. PMID: 10085249.
      View in: PubMed
    51. Hinchcliffe EH, Li C, Thompson EA, Maller JL, Sluder G. Requirement of Cdk2-cyclin E activity for repeated centrosome reproduction in Xenopus egg extracts. Science. 1999 Feb 5; 283(5403):851-4. PMID: 9933170.
      View in: PubMed
    52. Sluder G, Miller FJ, Hinchcliffe EH. Using sea urchin gametes for the study of mitosis. Methods Cell Biol. 1999; 61:439-72. PMID: 9891327.
      View in: PubMed
    53. Hinchcliffe EH, Cassels GO, Rieder CL, Sluder G. The coordination of centrosome reproduction with nuclear events of the cell cycle in the sea urchin zygote. J Cell Biol. 1998 Mar 23; 140(6):1417-26. PMID: 9508774.
      View in: PubMed
    54. Sluder G, Hinchcliffe EH. Video basics: use of camera and monitor adjustments. Methods Cell Biol. 1998; 56:1-17. PMID: 9500130.
      View in: PubMed
    55. Sluder G, Hinchcliffe EH. The apparent linkage between centriole replication and the S phase of the cell cycle. Cell Biol Int. 1998; 22(1):3-5. PMID: 9828076.
      View in: PubMed
    56. Wheatley SP, Hinchcliffe EH, Glotzer M, Hyman AA, Sluder G, Wang Yl. CDK1 inactivation regulates anaphase spindle dynamics and cytokinesis in vivo. J Cell Biol. 1997 Jul 28; 138(2):385-93. PMID: 9230080.
      View in: PubMed
    57. Rieder CL, Khodjakov A, Paliulis LV, Fortier TM, Cole RW, Sluder G. Mitosis in vertebrate somatic cells with two spindles: implications for the metaphase/anaphase transition checkpoint and cleavage. Proc Natl Acad Sci U S A. 1997 May 13; 94(10):5107-12. PMID: 9144198.
      View in: PubMed
    58. Sluder G, Thompson EA, Miller FJ, Hayes J, Rieder CL. The checkpoint control for anaphase onset does not monitor excess numbers of spindle poles or bipolar spindle symmetry. J Cell Sci. 1997 Feb; 110 ( Pt 4):421-9. PMID: 9067594.
      View in: PubMed
    59. Sluder G, Rieder CL. Controls for centrosome reproduction in animal cells: issues and recent observations. Cell Motil Cytoskeleton. 1996; 33(1):1-5. PMID: 8824729.
      View in: PubMed
    60. Rieder CL, Cole RW, Khodjakov A, Sluder G. The checkpoint delaying anaphase in response to chromosome monoorientation is mediated by an inhibitory signal produced by unattached kinetochores. J Cell Biol. 1995 Aug; 130(4):941-8. PMID: 7642709.
      View in: PubMed
    61. Sluder G, Thompson EA, Rieder CL, Miller FJ. Nuclear envelope breakdown is under nuclear not cytoplasmic control in sea urchin zygotes. J Cell Biol. 1995 Jun; 129(6):1447-58. PMID: 7790347.
      View in: PubMed
    62. Rieder CL, Schultz A, Cole R, Sluder G. Anaphase onset in vertebrate somatic cells is controlled by a checkpoint that monitors sister kinetochore attachment to the spindle. J Cell Biol. 1994 Dec; 127(5):1301-10. PMID: 7962091.
      View in: PubMed
    63. Sluder G, Miller FJ, Thompson EA, Wolf DE. Feedback control of the metaphase-anaphase transition in sea urchin zygotes: role of maloriented chromosomes. J Cell Biol. 1994 Jul; 126(1):189-98. PMID: 8027177.
      View in: PubMed
    64. Sluder G, Miller FJ, Lewis K. Centrosome inheritance in starfish zygotes. II: Selective suppression of the maternal centrosome during meiosis. Dev Biol. 1993 Jan; 155(1):58-67. PMID: 8416845.
      View in: PubMed
    65. Sluder G. Double or nothing. Curr Biol. 1992 May; 2(5):243-5. PMID: 15335959.
      View in: PubMed
    66. Sluder G, Miller FJ, Cole R, Rieder CL. Protein synthesis and the cell cycle: centrosome reproduction in sea urchin eggs is not under translational control. J Cell Biol. 1990 Jun; 110(6):2025-32. PMID: 2351692.
      View in: PubMed
    67. Sluder G. Functional properties of kinetochores in animal cells. Curr Opin Cell Biol. 1990 Feb; 2(1):23-7. PMID: 2183838.
      View in: PubMed
    68. Sluder G, Miller FJ, Lewis K, Davison ED, Rieder CL. Centrosome inheritance in starfish zygotes: selective loss of the maternal centrosome after fertilization. Dev Biol. 1989 Feb; 131(2):567-79. PMID: 2912809.
      View in: PubMed
    69. Sluder G. Centrosomes and the cell cycle. J Cell Sci Suppl. 1989; 12:253-75. PMID: 2635706.
      View in: PubMed
    70. Sluder G, Miller FJ, Rieder CL. Reproductive capacity of sea urchin centrosomes without centrioles. Cell Motil Cytoskeleton. 1989; 13(4):264-73. PMID: 2776224.
      View in: PubMed
    71. Sluder G, Lewis K. Relationship between nuclear DNA synthesis and centrosome reproduction in sea urchin eggs. J Exp Zool. 1987 Oct; 244(1):89-100. PMID: 3694143.
      View in: PubMed
    72. Sluder G, Miller FJ, Rieder CL. The reproduction of centrosomes: nuclear versus cytoplasmic controls. J Cell Biol. 1986 Nov; 103(5):1873-81. PMID: 3782286.
      View in: PubMed
    73. Sluder G, Miller FJ, Spanjian K. The role of spindle microtubules in the timing of the cell cycle in echinoderm eggs. J Exp Zool. 1986 Jun; 238(3):325-36. PMID: 3723088.
      View in: PubMed
    74. Sluder G, Miller FJ, Rieder CL. Centrosomes are required for the assembly of a bipolar spindle in animal cells. Ann N Y Acad Sci. 1986; 466:669-73. PMID: 3460442.
      View in: PubMed
    75. Sluder G, Rieder CL. Centriole number and the reproductive capacity of spindle poles. J Cell Biol. 1985 Mar; 100(3):887-96. PMID: 3972899.
      View in: PubMed
    76. Sluder G, Rieder CL. Experimental separation of pronuclei in fertilized sea urchin eggs: chromosomes do not organize a spindle in the absence of centrosomes. J Cell Biol. 1985 Mar; 100(3):897-903. PMID: 3972900.
      View in: PubMed
    77. Sluder G, Begg DA. Control mechanisms of the cell cycle: role of the spatial arrangement of spindle components in the timing of mitotic events. J Cell Biol. 1983 Sep; 97(3):877-86. PMID: 6885924.
      View in: PubMed
    78. Sluder G. Role of spindle microtubules in the control of cell cycle timing. J Cell Biol. 1979 Mar; 80(3):674-91. PMID: 572367.
      View in: PubMed
    79. Sluder G. Experimental manipulation of the amount of tubulin available for assembly into the spindle of dividing sea urchin eggs. J Cell Biol. 1976 Jul; 70(1):75-85. PMID: 945280.
      View in: PubMed
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