Darwin, mais design: mecânica cromossômica "guia" a montagem nuclear

quarta-feira, outubro 04, 2017

Cell Volume 170, Issue 5, 24 August 2017, Pages 956-972.e23


DNA Cross-Bridging Shapes a Single Nucleus from a Set of Mitotic Chromosomes ReadCube 

MatthiasSamwer1 Maximilian W.G.Schneider1 RudolfHoefler1 Philipp S.Schmalhorst2 Julian G.Jude3 JohannesZuber3 Daniel W.Gerlich14

1 Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), 1030 Vienna, Austria

2 Institute of Science and Technology Austria (IST Austria), 3400 Klosterneuburg, Austria

3 Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria

Received 2 March 2017, Revised 12 June 2017, Accepted 24 July 2017, Available online 25 August 2017.

Published: August 24, 2017

Open Access funded by European Research Council

Under a Creative Commons licenseopen access


• Spindle-independent mechanism based on BAF shapes single nucleus in mitotic exit

• BAF transiently cross-bridges anaphase chromosomes to prevent nuclear fragmentation

• BAF forms a dense DNA network at the chromosome ensemble surface

• Network mesh size restricts membrane access and thereby guides the nuclear envelope


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.


mitosis nuclear assembly chromosomes nuclear envelope micronuclei chromothripsis barrier-to-autointegration factor BAF DNA cross-bridging