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Towards building a chromosome segregation machine

Abstract

All organisms, from bacteria to humans, face the daunting task of replicating, packaging and segregating up to two metres (about 6 × 109 base pairs) of DNA when each cell divides. This task is carried out up to a trillion times during the development of a human from a single fertilized cell. The strategy by which DNA is replicated is now well understood. But when it comes to packaging and segregating a genome, the mechanisms are only beginning to be understood and are often as variable as the organisms in which they are studied.

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Figure 1: Modes of chromosome segregation in prokaryotes and eukaryotes.
Figure 2: Chromosomal loops.
Figure 3: SMC-protein-containing rings and the distribution of force.
Figure 4: Protein architecture of the Saccharomyces cerevisiae kinetochore.
Figure 5: Proposed mechanisms for microtubule-depolymerization-coupled force generation at the kinetochore.

References

  1. 1

    Mogilner, A. & Oster, G. Polymer motors: pushing out the front and pulling up the back. Curr. Biol. 13, R721–R733 (2003).

  2. 2

    Wolgemuth, C. W., Mogilner, A. & Oster, G. The hydration dynamics of polyelectrolyte gels with applications to cell motility and drug delivery. Eur. Biophys. J. 33, 146–158 (2004).

    PubMed  Article  CAS  Google Scholar 

  3. 3

    Mazumder, A. & Shivashankar, G. V. Gold-nanoparticle-assisted laser perturbation of chromatin assembly reveals unusual aspects of nuclear architecture within living cells. Biophys. J. 93, 2209–2216 (2007).

    ADS  PubMed  PubMed Central  Article  CAS  Google Scholar 

  4. 4

    Mazumder, A., Roopa, T., Basu, A., Mahadevan, L. & Shivashankar, G. V. Dynamics of chromatin decondensation reveals the structural integrity of a mechanically prestressed nucleus. Biophys. J. 95, 3028–3035 (2008).

    ADS  PubMed  PubMed Central  Article  CAS  Google Scholar 

  5. 5

    Jun, S. & Mulder, B. Entropy-driven spatial organization of highly confined polymers: lessons for the bacterial chromosome. Proc. Natl Acad. Sci. USA 103, 12388–12393 (2006).

    ADS  PubMed  Article  CAS  Google Scholar 

  6. 6

    Rao, V. B. & Feiss, M. The bacteriophage DNA packaging motor. Annu. Rev. Genet. 42, 647–681 (2008).

    PubMed  Article  CAS  Google Scholar 

  7. 7

    Finzi, L. & Gelles, J. Measurement of lactose repressor-mediated loop formation and breakdown in single DNA molecules. Science 267, 378–380 (1995).

    ADS  PubMed  Article  CAS  Google Scholar 

  8. 8

    Bianco, P. R. et al. Processive translocation and DNA unwinding by individual RecBCD enzyme molecules. Nature 409, 374–378 (2001).

    ADS  PubMed  Article  CAS  Google Scholar 

  9. 9

    Wang, M. D. et al. Force and velocity measured for single molecules of RNA polymerase. Science 282, 902–907 (1998).

    ADS  PubMed  Article  CAS  Google Scholar 

  10. 10

    Yin, H. et al. Transcription against an applied force. Science 270, 1653–1657 (1995).

    ADS  PubMed  Article  CAS  Google Scholar 

  11. 11

    Dworkin, J. & Losick, R. Does RNA polymerase help drive chromosome segregation in bacteria? Proc. Natl Acad. Sci. USA 99, 14089–14094 (2002).

    ADS  PubMed  Article  CAS  Google Scholar 

  12. 12

    Holm, C., Goto, T., Wang, J. C. & Botstein, D. DNA topoisomerase II is required at the time of mitosis in yeast. Cell 41, 553–563 (1985).

    PubMed  Article  CAS  Google Scholar 

  13. 13

    Emanuel, M., Radja, N. H., Henriksson, A. & Schiessel, H. The physics behind the larger scale organization of DNA in eukaryotes. Phys. Biol. 6, 25008 (2009).

  14. 14

    Towles, K. B., Beausang, J. F., Garcia, H. G., Phillips, R. & Nelson, P. C. First-principles calculation of DNA looping in tethered particle experiments. Phys. Biol. 6, 25001 (2009).

  15. 15

    Pope, L. H., Xiong, C. & Marko, J. F. Proteolysis of mitotic chromosomes induces gradual and anisotropic decondensation correlated with a reduction of elastic modulus and structural sensitivity to rarely cutting restriction enzymes. Mol. Biol. Cell 17, 104–113 (2006).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  16. 16

    Hirano, T. At the heart of the chromosome: SMC proteins in action. Nature Rev. Mol. Cell Biol. 7, 311–322 (2006).

    Article  CAS  Google Scholar 

  17. 17

    Yeh, E. et al. Pericentric chromatin is organized into an intramolecular loop in mitosis. Curr. Biol. 18, 81–90 (2008). Pericentromeric chromatin adopts an intramolecular loop that is stretched between sister centromeres in mitosis. It is proposed that these loops function as DNA springs in the mitotic spindle.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  18. 18

    Doi, M. & Edwards, S. The Theory of Polymer Dynamics (Oxford Univ. Press, 1992).

    Google Scholar 

  19. 19

    Okumura, Y. & Ito, K. The Polyrotaxane gel: a topological gel by figure-of-eight cross-links. Adv. Mater. 13, 485–487 (2001).

    Article  CAS  Google Scholar 

  20. 20

    Daneholt, B., Anderson, K. & Fagerlind, M. Large-sized polysomes in Chironomus tentans salivary glands and their relation to Balbiani ring 75S. RNA. J. Cell Biol. 73, 149–160 (1977).

    PubMed  Article  CAS  Google Scholar 

  21. 21

    Gall, J. G. in Methods in Cell Physiology Vol. II (ed. Prescott, D. M.) 37–60 (Academic, 1966).

    Google Scholar 

  22. 22

    Paulson, J. R. & Laemmli, U. K. The structure of histone-depleted metaphase chromosomes. Cell 12, 817–828 (1977).

    PubMed  Article  CAS  Google Scholar 

  23. 23

    Sullivan, N. L., Marquis, K. A. & Rudner, D. Z. Recruitment of SMC by ParB–ParS organizes the origin region and promotes efficient chromosome segregation. Cell 137, 697–707 (2009). This study shows that SMC protein components localize to the origin of replication in B. subtilis and demonstrates that chromosome condensation coupled to replication is a major mechanism of chromosome segregation in bacteria.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  24. 24

    Sumara, I., Vorlaufer, E., Gieffers, C., Peters, B. H. & Peters, J. M. Characterization of vertebrate cohesin complexes and their regulation in prophase. J. Cell Biol. 151, 749–762 (2000).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  25. 25

    Waizenegger, I. C., Hauf, S., Meinke, A. & Peters, J. M. Two distinct pathways remove mammalian cohesin from chromosome arms in prophase and from centromeres in anaphase. Cell 103, 399–410 (2000).

    PubMed  Article  CAS  Google Scholar 

  26. 26

    Harrison, B. D., Hoang, M. L. & Bloom, K. Persistent mechanical linkage between sister chromatids throughout anaphase. Chromosoma 118, 633–645 (2009).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  27. 27

    Paliulis, L. V. & Nicklas, R. B. Micromanipulation of chromosomes reveals that cohesion release during cell division is gradual and does not require tension. Curr. Biol. 14, 2124–2129 (2004).

    PubMed  Article  CAS  Google Scholar 

  28. 28

    Storlazzi, A. et al. Coupling meiotic chromosome axis integrity to recombination. Genes Dev. 22, 796–809 (2008).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  29. 29

    Obermayer, B., Mobius, W., Hallatschek, O., Frey, E. & Kroy, K. Freely relaxing polymers remember how they were straightened. Phys. Rev. E 79, 021804 (2009).

  30. 30

    Meaburn, K. J. & Misteli, T. Chromosome territories. Nature 445, 379–381 (2007).

    ADS  PubMed  Article  CAS  Google Scholar 

  31. 31

    Austin, S. & Abeles, A. Partition of unit-copy miniplasmids to daughter cells. II. The partition region of miniplasmid P1 encodes an essential protein and a centromere-like site at which it acts. J. Mol. Biol. 169, 373–387 (1983).

    PubMed  Article  CAS  Google Scholar 

  32. 32

    Ogura, T. & Hiraga, S. Partition mechanism of F plasmid: two plasmid gene-encoded products and a cis-acting region are involved in partition. Cell 32, 351–360 (1983).

    PubMed  Article  CAS  Google Scholar 

  33. 33

    Schumacher, M. A. Structural biology of plasmid partition: uncovering the molecular mechanisms of DNA segregation. Biochem. J. 412, 1–18 (2008).

    PubMed  Article  CAS  Google Scholar 

  34. 34

    Lynch, A. S. & Wang, J. C. Use of an inducible site-specific recombinase to probe the structure of protein–DNA complexes involved in F plasmid partition in Escherichia coli. J. Mol. Biol. 236, 679–684 (1994).

    PubMed  Article  CAS  Google Scholar 

  35. 35

    Clarke, L. & Carbon, J. Isolation of a yeast centromere and construction of functional small circular chromosomes. Nature 287, 504–509 (1980).

    ADS  PubMed  Article  CAS  Google Scholar 

  36. 36

    Furuyama, T. & Henikoff, S. Centromeric nucleosomes induce positive DNA supercoils. Cell 138, 104–113 (2009). This paper reports that the direction of DNA coiling around histone complexes containing the centromere-specific histone variant CENP-A is opposite to the canonical negative supercoils around histones. This is one of several features that distinguish centromeric chromatin from the rest of the genome.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  37. 37

    Strahl, B. D. & Allis, C. D. The language of covalent histone modifications. Nature 403, 41–45 (2000).

    ADS  PubMed  Article  CAS  Google Scholar 

  38. 38

    Dalal, Y., Furuyama, T., Vermaak, D. & Henikoff, S. Structure, dynamics, and evolution of centromeric nucleosomes. Proc. Natl Acad. Sci. USA 104, 15974–15981 (2007).

    ADS  PubMed  Article  Google Scholar 

  39. 39

    Dalal, Y., Wang, H., Lindsay, S. & Henikoff, S. Tetrameric structure of centromeric nucleosomes in interphase Drosophila cells. PLoS Biol. 5, e218 (2007).

  40. 40

    Hill, A. & Bloom, K. Genetic manipulation of centromere function. Mol. Cell. Biol. 7, 2397–2405 (1987).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  41. 41

    Collins, K. A., Castillo, A. R., Tatsutani, S. Y. & Biggins, S. De novo kinetochore assembly requires the centromeric histone H3 variant. Mol. Biol. Cell 16, 5649–5660 (2005).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  42. 42

    Hamiche, A. et al. Interaction of the histone (H3−H4)2 tetramer of the nucleosome with positively supercoiled DNA minicircles: potential flipping of the protein from a left- to a right-handed superhelical form. Proc. Natl Acad. Sci. USA 93, 7588–7593 (1996).

    ADS  PubMed  Article  CAS  Google Scholar 

  43. 43

    Bancaud, A. et al. Nucleosome chiral transition under positive torsional stress in single chromatin fibers. Mol. Cell 27, 135–147 (2007).

    PubMed  Article  CAS  Google Scholar 

  44. 44

    Selvin, P. R. et al. Torsional rigidity of positively and negatively supercoiled DNA. Science 255, 82–85 (1992).

    ADS  PubMed  CAS  Google Scholar 

  45. 45

    Bloom, K. S. & Carbon, J. Yeast centromere DNA is in a unique and highly ordered structure in chromosomes and small circular minichromosomes. Cell 29, 305–317 (1982).

    PubMed  Article  CAS  Google Scholar 

  46. 46

    Folco, H. D., Pidoux, A. L., Urano, T. & Allshire, R. C. Heterochromatin and RNAi are required to establish CENP-A chromatin at centromeres. Science 319, 94–97 (2008).

    ADS  PubMed  PubMed Central  Article  CAS  Google Scholar 

  47. 47

    Blat, Y. & Kleckner, N. Cohesins bind to preferential sites along yeast chromosome III, with differential regulation along arms versus the centric region. Cell 98, 249–259 (1999).

    PubMed  Article  CAS  Google Scholar 

  48. 48

    Weber, S. A. et al. The kinetochore is an enhancer of pericentric cohesin binding. PLoS Biol. 2, e260 (2004).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  49. 49

    Eckert, C. A., Gravdahl, D. J. & Megee, P. C. The enhancement of pericentromeric cohesin association by conserved kinetochore components promotes high-fidelity chromosome segregation and is sensitive to microtubule-based tension. Genes Dev. 21, 278–291 (2007).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  50. 50

    Haldar, D. & Kamakaka, R. T. tRNA genes as chromatin barriers. Nature Struct. Mol. Biol. 13, 192–193 (2006).

    Article  CAS  Google Scholar 

  51. 51

    He, X., Asthana, S. & Sorger, P. K. Transient sister chromatid separation and elastic deformation of chromosomes during mitosis in budding yeast. Cell 101, 763–775 (2000).

    PubMed  Article  CAS  Google Scholar 

  52. 52

    Pearson, C. G., Maddox, P. S., Salmon, E. D. & Bloom, K. Budding yeast chromosome structure and dynamics during mitosis. J. Cell Biol. 152, 1255–1266 (2001).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  53. 53

    Ribeiro, S. A. et al. Condensin regulates the stiffness of vertebrate centromeres. Mol. Biol. Cell 20, 2371–2380 (2009).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  54. 54

    Skibbens, R. V., Skeen, V. P. & Salmon, E. D. Directional instability of kinetochore motility during chromosome congression and segregation in mitotic newt lung cells: a push–pull mechanism. J. Cell Biol. 122, 859–875 (1993).

    PubMed  Article  CAS  Google Scholar 

  55. 55

    Maresca, T. J. & Salmon, E. D. Intrakinetochore stretch is associated with changes in kinetochore phosphorylation and spindle assembly checkpoint activity. J. Cell Biol. 184, 373–381 (2009).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  56. 56

    Uchida, K. S. et al. Kinetochore stretching inactivates the spindle assembly checkpoint. J. Cell Biol. 184, 383–390 (2009).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  57. 57

    Bouck, D. C. & Bloom, K. Pericentric chromatin is an elastic component of the mitotic spindle. Curr. Biol. 17, 741–748 (2007). This paper shows that the level of nucleosomal DNA compaction regulates the length of the mitotic spindle.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  58. 58

    Zocchi, G. Controlling proteins through molecular springs. Annu. Rev. Biophys. 38, 75–88 (2009). This review discusses how the elastic energy of the DNA spring can induce a conformational change in a protein through the construction of a novel protein-DNA chimaera.

    PubMed  Article  CAS  Google Scholar 

  59. 59

    Zelin, E. & Silverman, S. K. Allosteric control of ribozyme catalysis by using DNA constraints. ChemBioChem 8, 1907–1911 (2007).

    PubMed  Article  CAS  Google Scholar 

  60. 60

    Ocampo-Hafalla, M. T., Katou, Y., Shirahige, K. & Uhlmann, F. Displacement and re-accumulation of centromeric cohesin during transient pre-anaphase centromere splitting. Chromosoma 116, 531–544 (2007).

    PubMed  PubMed Central  Article  Google Scholar 

  61. 61

    Gerlich, D., Hirota, T., Koch, B., Peters, J. M. & Ellenberg, J. Condensin I stabilizes chromosomes mechanically through a dynamic interaction in live cells. Curr. Biol. 16, 333–344 (2006).

    PubMed  Article  CAS  Google Scholar 

  62. 62

    Oliveira, R. A., Coelho, P. A. & Sunkel, C. E. The condensin I subunit Barren/CAP-H is essential for the structural integrity of centromeric heterochromatin during mitosis. Mol. Cell Biol. 25, 8971–8984 (2005).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  63. 63

    Fisher, J. K. et al. DNA relaxation dynamics as a probe for the intracellular environment. Proc. Natl Acad. Sci. USA 106, 9250–9255 (2009).

    ADS  PubMed  Article  Google Scholar 

  64. 64

    Callaway, E. Bacteria's new bones. Nature 451, 124–126 (2008).

    ADS  PubMed  Article  CAS  Google Scholar 

  65. 65

    Cordova, N. J., Ermentrout, B. & Oster, G. F. Dynamics of single-motor molecules: the thermal ratchet model. Proc. Natl Acad. Sci. USA 89, 339–343 (1992).

    ADS  PubMed  Article  CAS  Google Scholar 

  66. 66

    Garner, E. C., Campbell, C. S., Weibel, D. B. & Mullins, R. D. Reconstitution of DNA segregation driven by assembly of a prokaryotic actin homolog. Science 315, 1270–1274 (2007). This paper shows that prokaryotic DNA segregation can be reconstituted in vitro with defined components. The mechanism of segregation is polymer growth at the sites of contact with the DNA.

    ADS  PubMed  PubMed Central  Article  CAS  Google Scholar 

  67. 67

    Ramamurthi, K. S. & Losick, R. Grasping at origins. Cell 134, 916–918 (2008).

    PubMed  Article  CAS  Google Scholar 

  68. 68

    Bowman, G. R. et al. A polymeric protein anchors the chromosomal origin/ParB complex at a bacterial cell pole. Cell 134, 945–955 (2008).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  69. 69

    Ebersbach, G., Briegel, A., Jensen, G. J. & Jacobs-Wagner, C. A self-associating protein critical for chromosome attachment, division, and polar organization in Caulobacter. Cell 134, 956–968 (2008).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  70. 70

    Marquis, K. A. et al. SpoIIIE strips proteins off the DNA during chromosome translocation. Genes Dev. 22, 1786–1795 (2008).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  71. 71

    Ptacin, J. L. et al. Sequence-directed DNA export guides chromosome translocation during sporulation in Bacillus subtilis. Nature Struct. Mol. Biol. 15, 485–493 (2008).

    Article  CAS  Google Scholar 

  72. 72

    Walczak, C. E. & Heald, R. Mechanisms of mitotic spindle assembly and function. Int. Rev. Cytol. 265, 111–158 (2008).

    PubMed  Article  CAS  Google Scholar 

  73. 73

    Cottingham, F. R., Gheber, L., Miller, D. L. & Hoyt, M. A. Novel roles for Saccharomyces cerevisiae mitotic spindle motors. J. Cell Biol. 147, 335–350 (1999).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  74. 74

    Welburn, J. P. & Cheeseman, I. M. Toward a molecular structure of the eukaryotic kinetochore. Dev. Cell 15, 645–655 (2008).

    PubMed  Article  CAS  Google Scholar 

  75. 75

    Joglekar, A. P., Bloom, K. & Salmon, E. D. In vivo protein architecture of the eukaryotic kinetochore with nanometer scale accuracy. Curr. Biol. 19, 694–699 (2009). This paper shows the protein architecture of the S. cerevisiae kinetochore in metaphase and anaphase, by using live-cell super-resolution microscopy of fluorescently labelled kinetochore proteins.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  76. 76

    Wan, X. et al. Protein architecture of the human kinetochore microtubule attachment site. Cell 137, 672–684 (2009). This study used two-colour super-resolution microscopy to visualize fixed HeLa cells stained with antibodies, allowing the spatial position of proteins in the mammalian kinetochore to be determined with nanometre accuracy.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  77. 77

    Hill, T. L. Theoretical problems related to the attachment of microtubules to kinetochores. Proc. Natl Acad. Sci. USA 82, 4404–4408 (1985).

    ADS  PubMed  Article  CAS  Google Scholar 

  78. 78

    Desai, A. & Mitchison, T. J. Microtubule polymerization dynamics. Annu. Rev. Cell Dev. Biol. 13, 83–117 (1997).

    PubMed  Article  CAS  Google Scholar 

  79. 79

    Miranda, J. J., De Wulf, P., Sorger, P. K. & Harrison, S. C. The yeast DASH complex forms closed rings on microtubules. Nature Struct. Mol. Biol. 12, 138–143 (2005).

    Article  CAS  Google Scholar 

  80. 80

    Westermann, S. et al. Formation of a dynamic kinetochore–microtubule interface through assembly of the Dam1 ring complex. Mol. Cell 17, 277–290 (2005).

    PubMed  Article  CAS  Google Scholar 

  81. 81

    Efremov, A., Grishchuk, E. L., McIntosh, J. R. & Ataullakhanov, F. I. In search of an optimal ring to couple microtubule depolymerization to processive chromosome motions. Proc. Natl Acad. Sci. USA 104, 19017–19022 (2007).

    ADS  PubMed  Article  Google Scholar 

  82. 82

    Grishchuk, E. L. et al. The Dam1 ring binds microtubules strongly enough to be a processive as well as energy-efficient coupler for chromosome motion. Proc. Natl Acad. Sci. USA 105, 15423–15428 (2008).

    ADS  PubMed  Article  Google Scholar 

  83. 83

    Grishchuk, E. L. et al. Different assemblies of the DAM1 complex follow shortening microtubules by distinct mechanisms. Proc. Natl Acad. Sci. USA 105, 6918–6923 (2008).

    ADS  PubMed  Article  Google Scholar 

  84. 84

    McIntosh, J. R. et al. Fibrils connect microtubule tips with kinetochores: a mechanism to couple tubulin dynamics to chromosome motion. Cell 135, 322–333 (2008).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  85. 85

    Asbury, C. L., Gestaut, D. R., Powers, A. F., Franck, A. D. & Davis, T. N. The Dam1 kinetochore complex harnesses microtubule dynamics to produce force and movement. Proc. Natl Acad. Sci. USA 103, 9873–9878 (2006).

    ADS  PubMed  Article  CAS  Google Scholar 

  86. 86

    Powers, A. F. et al. The Ndc80 kinetochore complex forms load-bearing attachments to dynamic microtubule tips via biased diffusion. Cell 136, 865–875 (2009).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  87. 87

    Nicklas, R. B. The forces that move chromosomes in mitosis. Annu. Rev. Biophys. Biophys. Chem. 17, 431–449 (1988).

    Article  CAS  Google Scholar 

  88. 88

    Mehta, S. et al. The 2 micron plasmid purloins the yeast cohesin complex: a mechanism for coupling plasmid partitioning and chromosome segregation? J. Cell Biol. 158, 625–637 (2002).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  89. 89

    Kiermaier, E., Woehrer, S., Peng, Y., Mechtler, K. & Westermann, S. A. Dam1-based artificial kinetochore is sufficient to promote chromosome segregation in budding yeast. Nature Cell Biol. 11, 1109–1115 (2009).

    PubMed  Article  CAS  Google Scholar 

  90. 90

    Lacefield, S., Lau, D. T. & Murray, A. W. Recruiting a microtubule-binding complex to DNA directs chromosome segregation in budding yeast. Nature Cell Biol. 11, 1116–1120 (2009).

    PubMed  Article  CAS  Google Scholar 

  91. 91

    Hertwig, O. Lehrbuch der Entwicklungsgeschichte des Menschen und der Wirbeltiere (Fischer, 1906).

    Google Scholar 

  92. 92

    Zinkowski, R. P., Meyne, J. & Brinkley, B. R. The centromere–kinetochore complex: a repeat subunit model. J. Cell Biol. 113, 1091–1110 (1991).

    PubMed  Article  CAS  Google Scholar 

  93. 93

    Hori, T. et al. CCAN makes multiple contacts with centromeric DNA to provide distinct pathways to the outer kinetochore. Cell 135, 1039–1052 (2008). This paper identifies kinetochore components that interact with nucleosomal DNA that does not contain the centromere-specific histone. This is a key finding for understanding how chromatin is organized within a mammalian centromere.

    PubMed  Article  CAS  Google Scholar 

  94. 94

    Miller, S. A., Johnson, M. L. & Stukenberg, P. T. Kinetochore attachments require an interaction between unstructured tails on microtubules and Ndc80 (Hec1). Curr. Biol. 18, 1785–1791 (2008).

  95. 95

    Guimaraes, G. J., Dong, Y., McEwen, B. F. & Deluca, J. G. Kinetochore–microtubule attachment relies on the disordered N-terminal tail domain of Hec1. Curr. Biol. 18, 1778–1784 (2008).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

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Acknowledgements

We thank E. Yeh, J. Haase and J. Verdaasdonk (Department of Biology, University of North Carolina at Chapel Hill) for comments on the manuscript, and L. Vicci and R. M. Taylor III (Department of Computer Science, University of North Carolina at Chapel Hill) and M. Rubinstein (Department of Chemistry, University of North Carolina at Chapel Hill) for discussions concerning the mechanical properties of biological molecules.

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Correspondence should be addressed to K.B. (kerry_bloom@unc.edu).

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Bloom, K., Joglekar, A. Towards building a chromosome segregation machine. Nature 463, 446–456 (2010). https://doi.org/10.1038/nature08912

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