Samwer, Matthias; Schneider, Maximilian; Hoefler, Rudolf; Schmalhorst, Philipp SIST Austria ; Jude, Julian; Zuber, Johannes; Gerlic, Daniel
Eukaryotic cells store their chromosomes in a single nucleus. This is important to maintain genomic integrity, as chromosomes packaged into separate nuclei (micronuclei) are prone to massive DNA damage. During mitosis, higher eukaryotes disassemble their nucleus and release individualized chromosomes for segregation. How numerous chromosomes subsequently reform a single nucleus has remained unclear. Using image-based screening of human cells, we identified barrier-to-autointegration factor (BAF) as a key factor guiding membranes to form a single nucleus. Unexpectedly, nuclear assembly does not require BAF?s association with inner nuclear membrane proteins but instead relies on BAF?s ability to bridge distant DNA sites. Live-cell imaging and in vitro reconstitution showed that BAF enriches around the mitotic chromosome ensemble to induce a densely cross-bridged chromatin layer that is mechanically stiff and limits membranes to the surface. Our study reveals that BAF-mediated changes in chromosome mechanics underlie nuclear assembly with broad implications for proper genome function.
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Samwer M, Schneider M, Hoefler R, et al. DNA cross-bridging shapes a single nucleus from a set of mitotic chromosomes. Cell. 2017;170(5):956-972. doi:10.1016/j.cell.2017.07.038
Samwer, M., Schneider, M., Hoefler, R., Schmalhorst, P. S., Jude, J., Zuber, J., & Gerlic, D. (2017). DNA cross-bridging shapes a single nucleus from a set of mitotic chromosomes. Cell. Cell Press. https://doi.org/10.1016/j.cell.2017.07.038
Samwer, Matthias, Maximilian Schneider, Rudolf Hoefler, Philipp S Schmalhorst, Julian Jude, Johannes Zuber, and Daniel Gerlic. “DNA Cross-Bridging Shapes a Single Nucleus from a Set of Mitotic Chromosomes.” Cell. Cell Press, 2017. https://doi.org/10.1016/j.cell.2017.07.038.
M. Samwer et al., “DNA cross-bridging shapes a single nucleus from a set of mitotic chromosomes,” Cell, vol. 170, no. 5. Cell Press, pp. 956–972, 2017.
Samwer M, Schneider M, Hoefler R, Schmalhorst PS, Jude J, Zuber J, Gerlic D. 2017. DNA cross-bridging shapes a single nucleus from a set of mitotic chromosomes. Cell. 170(5), 956–972.
Samwer, Matthias, et al. “DNA Cross-Bridging Shapes a Single Nucleus from a Set of Mitotic Chromosomes.” Cell, vol. 170, no. 5, Cell Press, 2017, pp. 956–72, doi:10.1016/j.cell.2017.07.038.
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