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Biased segregation of DNA and centrosomes — moving together or drifting apart?

Nature Reviews Molecular Cell Biology volume 10, pages 804–810 (2009)Cite this article

Abstract

Old and newly synthesized centrosomes have different microtubule nucleating abilities and they contribute to cell polarity when they migrate to opposite poles during cell division. The asymmetric localization of epigenetic marks and kinetochore proteins could lead to the differential recognition of sister chromatids and the biased segregation of DNA strands to daughter cells during cell division. We propose that this asymmetric localization is linked to biased chromatid segregation, which might also be related to the acquisition of distinct cell fates after mitosis.

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Figure 1: Biased centrosome segregation in Drosophila melanogaster stem cells.
Figure 2: Possible links between centrosomes and biased DNA segregation.
Figure 3: DNA replication is intrinsically asymmetric.

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References

  1. Knoblich, J. A. Mechanisms of asymmetric stem cell division. Cell 132, 583–597 (2008).

    Article  CAS  PubMed  Google Scholar 

  2. Uzbekov, R. & Prigent, C. Clockwise or anticlockwise? Turning the centriole triplets in the right direction! FEBS Lett. 581, 1251–1254 (2007).

    Article  CAS  PubMed  Google Scholar 

  3. Piel, M., Meyer, P., Khodjakov, A., Rieder, C. L. & Bornens, M. The respective contributions of the mother and daughter centrioles to centrosome activity and behavior in vertebrate cells. J. Cell Biol. 149, 317–330 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bettencourt-Dias, M. & Glover, D. M. Centrosome biogenesis and function: centrosomics brings new understanding. Nature Rev. Mol. Cell Biol. 8, 451–463 (2007).

    Article  CAS  Google Scholar 

  5. Yamashita, Y. M., Mahowald, A. P., Perlin, J. R. & Fuller, M. T. Asymmetric inheritance of mother versus daughter centrosome in stem cell division. Science 315, 518–521 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pereira, G., Tanaka, T. U., Nasmyth, K. & Schiebel, E. Modes of spindle pole body inheritance and segregation of the Bfa1p–Bub2p checkpoint protein complex. EMBO J. 20, 6359–6370 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Klar, A. J. Differentiated parental DNA strands confer developmental asymmetry on daughter cells in fission yeast. Nature 326, 466–470 (1987).

    Article  CAS  PubMed  Google Scholar 

  8. Klar, A. J. The developmental fate of fission yeast cells is determined by the pattern of inheritance of parental and grandparental DNA strands. EMBO J. 9, 1407–1415 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Klar, A. J. Lessons learned from studies of fission yeast mating-type switching and silencing. Annu. Rev. Genet. 41, 213–236 (2007).

    Article  CAS  PubMed  Google Scholar 

  10. Armakolas, A. & Klar, A. J. Cell type regulates selective segregation of mouse chromosome 7 DNA strands in mitosis. Science 311, 1146–1149 (2006).

    Article  CAS  PubMed  Google Scholar 

  11. Liu, P., Jenkins, N. A. & Copeland, N. G. Efficient Cre–loxP-induced mitotic recombination in mouse embryonic stem cells. Nature Genet. 30, 66–72 (2002).

    Article  CAS  PubMed  Google Scholar 

  12. Cairns, J. Mutation selection and the natural history of cancer. Nature 255, 197–200 (1975).

    Article  CAS  PubMed  Google Scholar 

  13. Klar, A. J. A model for specification of the left–right axis in vertebrates. Trends Genet. 10, 392–396 (1994).

    Article  CAS  PubMed  Google Scholar 

  14. Lansdorp, P. M. Immortal strands? Give me a break. Cell 129, 1244–1247 (2007).

    Article  CAS  PubMed  Google Scholar 

  15. Tajbakhsh, S. Stem cell identity and template DNA strand segregation. Curr. Opin. Cell Biol. 20, 716–722 (2008).

    Article  CAS  PubMed  Google Scholar 

  16. Yamashita, Y. M., Jones, D. L. & Fuller, M. T. Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome. Science 301, 1547–1550 (2003).

    Article  CAS  PubMed  Google Scholar 

  17. Stevens, N. R., Raposo, A. A., Basto, R., St. Johnston, D. & Raff, J. W. From stem cell to embryo without centrioles. Curr. Biol. 17, 1498–1503 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Varmark, H. et al. Asterless is a centriolar protein required for centrosome function and embryo development in Drosophila. Curr. Biol. 17, 1735–1745 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. Basto, R. et al. Flies without centrioles. Cell 125, 1375–1386 (2006).

    Article  CAS  PubMed  Google Scholar 

  20. Gonzalez, C. Centrosome function during stem cell division: the devil is in the details. Curr. Opin. Cell Biol. 20, 694–698 (2008).

    Article  CAS  PubMed  Google Scholar 

  21. Rusan, N. M. & Rogers, G. C. Centrosome function: Sometimes less is more. Traffic 10, 472–481 (2009).

    Article  CAS  PubMed  Google Scholar 

  22. Basto, R. et al. Centrosome amplification can initiate tumorigenesis in flies. Cell 133, 1032–1042 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Castellanos, E., Dominguez, P. & Gonzalez, C. Centrosome dysfunction in Drosophila neural stem cells causes tumors that are not due to genome instability. Curr. Biol. 18, 1209–1214 (2008).

    Article  CAS  PubMed  Google Scholar 

  24. Rebollo, E. et al. Functionally unequal centrosomes drive spindle orientation in asymmetrically dividing Drosophila neural stem cells. Dev. Cell 12, 467–474 (2007).

    Article  CAS  PubMed  Google Scholar 

  25. Rusan, N. M. & Peifer, M. A role for a novel centrosome cycle in asymmetric cell division. J. Cell Biol. 177, 13–20 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Stewart, E. J., Madden, R., Paul, G. & Taddei, F. Aging and death in an organism that reproduces by morphologically symmetric division. PLoS Biol. 3, e45 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Gitai, Z., Dye, N. A., Reisenauer, A., Wachi, M. & Shapiro, L. MreB actin-mediated segregation of a specific region of a bacterial chromosome. Cell 120, 329–341 (2005).

    Article  CAS  PubMed  Google Scholar 

  28. Huitema, E., Pritchard, S., Matteson, D., Radhakrishnan, S. K. & Viollier, P. H. Bacterial birth scar proteins mark future flagellum assembly site. Cell 124, 1025–1037 (2006).

    Article  CAS  PubMed  Google Scholar 

  29. Lam, H., Schofield, W. B. & Jacobs-Wagner, C. A landmark protein essential for establishing and perpetuating the polarity of a bacterial cell. Cell 124, 1011–1023 (2006).

    Article  CAS  PubMed  Google Scholar 

  30. White, M. A., Eykelenboom, J. K., Lopez-Vernaza, M. A., Wilson, E. & Leach, D. R. Non-random segregation of sister chromosomes in Escherichia coli. Nature 455, 1248–1250 (2008).

    Article  CAS  PubMed  Google Scholar 

  31. Lew, D. J., Burke, D. J. & Dutta, A. The immortal strand hypothesis: how could it work? Cell 133, 21–23 (2008).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sinclair, D. A. & Guarente, L. Extrachromosomal rDNA circles — a cause of aging in yeast. Cell 91, 1033–1042 (1997).

    Article  CAS  PubMed  Google Scholar 

  34. Shcheprova, Z., Baldi, S., Frei, S. B., Gonnet, G. & Barral, Y. A mechanism for asymmetric segregation of age during yeast budding. Nature 454, 728–734 (2008).

    Article  CAS  PubMed  Google Scholar 

  35. Karpowicz, P. et al. The germline stem cells of Drosophila melanogaster partition DNA non-randomly. Eur. J. Cell Biol. 88, 397–408 (2009).

    Article  CAS  PubMed  Google Scholar 

  36. Pimpinelli, S. & Ripoll, P. Nonrandom segregation of centromeres following mitotic recombination in Drosophila melanogaster. Proc. Natl Acad. Sci. USA 83, 3900–3903 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cairns, J. Cancer and the immortal strand hypothesis. Genetics 174, 1069–1072 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Rando, T. A. The immortal strand hypothesis: segregation and reconstruction. Cell 129, 1239–1243 (2007).

    Article  CAS  PubMed  Google Scholar 

  39. Rossi, D. J. et al. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature 447, 725–729 (2007).

    Article  CAS  PubMed  Google Scholar 

  40. Fei, J. F. & Huttner, W. B. Nonselective sister chromatid segregation in mouse embryonic neocortical precursor cells. Cereb. Cortex 19, i49–i54 (2009).

    Article  PubMed  Google Scholar 

  41. Kiel, M. J. et al. Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU. Nature 449, 238–242 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Sotiropoulou, P. A., Candi, A. & Blanpain, C. The majority of multipotent epidermal stem cells do not protect their genome by asymmetrical chromosome segregation. Stem Cells 26, 2964–2973 (2008).

    Article  CAS  PubMed  Google Scholar 

  43. Waghmare, S. K. et al. Quantitative proliferation dynamics and random chromosome segregation of hair follicle stem cells. EMBO J. 27, 1309–1320 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Shinin, V., Gayraud-Morel, B., Gomes, D. & Tajbakhsh, S. Asymmetric division and cosegregation of template DNA strands in adult muscle satellite cells. Nature Cell Biol. 8, 677–682 (2006).

    Article  CAS  PubMed  Google Scholar 

  45. Karpowicz, P. et al. Support for the immortal strand hypothesis: neural stem cells partition DNA asymmetrically in vitro. J. Cell Biol. 170, 721–732 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Conboy, M. J., Karasov, A. O. & Rando, T. A. High incidence of non-random template strand segregation and asymmetric fate determination in dividing stem cells and their progeny. PLoS Biol. 5, e102 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Bailey, S. M., Goodwin, E. H., Meyne, J. & Cornforth, M. N. CO-FISH reveals inversions associated with isochromosome formation. Mutagenesis 11, 139–144 (1996).

    Article  CAS  PubMed  Google Scholar 

  48. Bell, C. D. Is mitotic chromatid segregation random? Histol. Histopathol. 20, 1313–1320 (2005).

    CAS  PubMed  Google Scholar 

  49. Jablonka, P. & Jablonka, E. Non-random sister chromatid segregation by cell type. J. Theor. Biol. 99, 427–436 (1982).

    Article  CAS  PubMed  Google Scholar 

  50. Patkin, E. L. Epigenetic mechanisms for primary differentiation in mammalian embryos. Int. Rev. Cytol. 216, 81–129 (2002).

    Article  CAS  PubMed  Google Scholar 

  51. Blow, J. J. & Hodgson, B. Replication licensing — defining the proliferative state? Trends Cell Biol. 12, 72–78 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Henikoff, S. Nucleosome destabilization in the epigenetic regulation of gene expression. Nature Rev. Genet. 9, 15–26 (2008).

    Article  CAS  PubMed  Google Scholar 

  53. Probst, A. V., Dunleavy, E. & Almouzni, G. Epigenetic inheritance during the cell cycle. Nature Rev. Mol. Cell Biol. 10, 192–206 (2009).

    Article  CAS  Google Scholar 

  54. Burhans, W. C. et al. Emetine allows identification of origins of mammalian DNA replication by imbalanced DNA synthesis, not through conservative nucleosome segregation. EMBO J. 10, 4351–4360 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Weintraub, H., Worcel, A. & Alberts, B. A model for chromatin based upon two symmetrically paired half-nucleosomes. Cell 9, 409–417 (1976).

    Article  CAS  PubMed  Google Scholar 

  56. Ekwall, K. Epigenetic control of centromere behaviour. Annu. Rev. Genet. 41, 63–81 (2007).

    Article  CAS  PubMed  Google Scholar 

  57. Malik, H.S. & Henikoff, S. Major evolutionary transitions in centromere complexity. Cell 138, 1067–1082 (2009).

    Article  CAS  PubMed  Google Scholar 

  58. Thorpe, P. H., Bruno, J. & Rothstein, R. Kinetochore asymmetry defines a single yeast lineage. Proc. Natl Acad. Sci. USA 106, 6673–6678 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Pardo- Manuel de Villena, F. & Sapienza, C. Nonrandom segregation during meiosis: the unfairness of females. Mamm. Genome 12, 331–339 (2001).

    Article  Google Scholar 

  60. Grava, S., Schaerer, F., Faty, M., Philippsen, P. & Barral, Y. Asymmetric recruitment of dynein to spindle poles and microtubules promotes proper spindle orientation in yeast. Dev. Cell 10, 425–439 (2006).

    Article  CAS  PubMed  Google Scholar 

  61. Higuchi, T. & Uhlmann, F. Stabilization of microtubule dynamics at anaphase onset promotes chromosome segregation. Nature 433, 171–176 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Liakopoulos, D., Kusch, J., Grava, S., Vogel, J. & Barral, Y. Asymmetric loading of Kar9 onto spindle poles and microtubules ensures proper spindle alignment. Cell 112, 561–574 (2003).

    Article  CAS  PubMed  Google Scholar 

  63. Louie, R. K. et al. Adenomatous polyposis coli and EB1 localize in close proximity of the mother centriole and EB1 is a functional component of centrosomes. J. Cell Sci. 117, 1117–1128 (2004).

    Article  CAS  PubMed  Google Scholar 

  64. Armakolas, A. & Klar, A. J. Left–right dynein motor implicated in selective chromatid segregation in mouse cells. Science 315, 100–101 (2007).

    Article  CAS  PubMed  Google Scholar 

  65. Maiato, H., Rieder, C. L. & Khodjakov, A. Kinetochore-driven formation of kinetochore fibers contributes to spindle assembly during animal mitosis. J. Cell Biol. 167, 831–840 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kapoor, T. M. et al. Chromosomes can congress to the metaphase plate before biorientation. Science 311, 388–391 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Volpe, T. A. et al. Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297, 1833–1837 (2002).

    Article  CAS  PubMed  Google Scholar 

  68. Fuchs, E., Tumbar, T. & Guasch, G. Socializing with the neighbors: stem cells and their niche. Cell 116, 769–778 (2004).

    Article  CAS  PubMed  Google Scholar 

  69. Wilson, A. et al. Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell 135, 1118–1129 (2008).

    Article  CAS  PubMed  Google Scholar 

  70. Potten, C. S. & Booth, C. Keratinocyte stem cells: a commentary. J. Invest. Dermatol. 119, 888–899 (2002).

    Article  CAS  PubMed  Google Scholar 

  71. Barker, N. et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449, 1003–1007 (2007).

    Article  CAS  PubMed  Google Scholar 

  72. Luders, J. & Stearns, T. Microtubule-organizing centres: a re-evaluation. Nature Rev. Mol. Cell Biol. 8, 161–167 (2007).

    Article  Google Scholar 

  73. Carmena, M. & Earnshaw, W. C. The cellular geography of aurora kinases. Nature Rev. Mol. Cell Biol. 4, 842–854 (2003).

    Article  CAS  Google Scholar 

  74. Chang, P. & Stearns, T. Δ-tubulin and ɛ-tubulin: two new human centrosomal tubulins reveal new aspects of centrosome structure and function. Nature Cell Biol. 2, 30–35 (2000).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

S.T. would like to acknowledge support from the Institut Pasteur, Agence Nationale de la Recherche, EuroSystem (EU FP7) and the Fondation pour la Recherche Medicale. C.G.'s laboratory is supported by the European Union (ONCASYM-037398 FP6), the Spanish government (BFU2009-07975, Consolider-Ingenio2010 CENTROSOME_3D) and Generalitat de Catalunya (23SGR2005).

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  1. Shahragim Tajbakhsh is at the Stem Cells and Development Department of Developmental Biology, Institut Pasteur, CNRS URA 2578, 25 rue du Dr. Roux, 75724 Paris, Cedex 15, France.,

    Shahragim Tajbakhsh

  2. Cayetano Gonzalez is at the Cell Division Laboratory, Institut de Recerca Biomedica, PCB. C/ Baldiri Reixac 10–12, 08028 Barcelona, Spain and the Institucio Catalana de Recerca i Estudis Avançats, Passeig Lluis Companys 23, 08010 Barcelona, Spain. shaht@pasteur.fr; gonzalez@irbbarcelona.org,

    Cayetano Gonzalez

  3. gonzalez@irbbarcelona.org,

    Cayetano Gonzalez

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41580_2009_BFnrm2784_MOESM2_ESM.pdf

Supplementary information S1 (Box) | Stem cell self-renewal and altruistic suicide – a dual role for centrosomes? (PDF 609 kb)

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Tajbakhsh, S., Gonzalez, C. Biased segregation of DNA and centrosomes — moving together or drifting apart?. Nat Rev Mol Cell Biol 10, 804–810 (2009). https://doi.org/10.1038/nrm2784

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