Book of Abstracts: Albany 2011

category image Albany 2011
Conversation 17
June 14-18 2011
©Adenine Press (2010)

How is a long strand of DNA compacted into a chromosome?

Mitotic chromosomes are essential structures for the faithful transmission of duplicated genomic DNA into two daughter cells during cell division (1). A long strand of DNA is wrapped around the core histone and forms a nucleosome. The nucleosome has long been assumed to be folded into 30-nm chromatin fibers (Fig. A)(1). However, it remains unclear how the nucleosome or 30-nm chromatin fiber is organized into mitotic chromosomes, although it is well known that condensins and topoisomerase IIα are implicated in this process (2-4). When we observed frozen hydrated (vitrified) human mitotic cells using cryo-electron microscopy, which enables direct high-resolution imaging of the cellular structures in a close-to-native state, we did not find any higher order structures, or even 30-nm chromatin fibers, but just a uniform disordered texture of the chromosome (Fig. B) (5-6). To further investigate the structure of mitotic chromosome, we performed small angle x-ray scattering or SAXS, which can detect regular internal structures in non-crystalline materials in solution. Mitotic chromosomes purified from HeLa cells were exposed to the synchrotron radiation beam at SPring-8 in Japan. Again, the results were striking: no structural peaks larger than 11-nm were detected. Therefore, we propose that the nucleosome fibers exist in a highly disordered, interdigitated state like a “polymer melt” that undergoes local dynamic movement (Fig. B)(5-6). We also postulate that a similar state exists in active interphase nuclei, resulting in several advantages in the transcription and DNA replication processes (6-7). The possible genomic organization in the mitotic chromosomes and nuclei is discussed.

  1. B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts and P. Walter. Molecular Biology of the Cell, Garland, NY. (2007).
  2. J. R. Swedlow and T. Hirano. Mol Cell 11, 557-569 (2003).
  3. S. Ohta, L. Wood, J. C. Bukowski-Wills, J. Rappsilber and W. C. Earnshaw. Curr Opin Cell Biol 23, 114-121 (2010).
  4. K. Maeshima, S. Hihara and H. Takata. Cold Spring Harb Symp Quant Biol. 75 (2011), in press.
  5. M. Eltsov, K. M. Maclellan, K. Maeshima, A. S. Frangakis and J. Dubochet. Proc Natl Acad Sci U S A 105, 19732-19737 (2008).
  6. K. Maeshima, S. Hihara and M. Eltsov. Curr Opin Cell Biol 22, 291-297 (2010).
  7. E. Fussner, R. W. Ching and D. P. Bazett-Jones. Trends Biochem Sci 36, 1-6 (2011).

Kazuhiro Maeshima

Biological Macromolecules Laboratory Structural Biology Center National Institute of Genetics, Mishima, JapanL