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Cell. 2017 Aug 24;170(5):956-972.e23. doi: 10.1016/j.cell.2017.07.038.

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

Author information

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.
4
Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), 1030 Vienna, Austria. Electronic address: daniel.gerlich@imba.oeaw.ac.at.

Abstract

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.

KEYWORDS:

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

PMID:
28841419
PMCID:
PMC5638020
DOI:
10.1016/j.cell.2017.07.038
[Indexed for MEDLINE]
Free PMC Article

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