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

Autor:	Samwer M; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), 1030 Vienna, Austria., Schneider MWG; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), 1030 Vienna, Austria., Hoefler R; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), 1030 Vienna, Austria., Schmalhorst PS; Institute of Science and Technology Austria (IST Austria), 3400 Klosterneuburg, Austria., Jude JG; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria., Zuber J; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria., Gerlich DW; 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.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2017 Aug 24; Vol. 170 (5), pp. 956-972.e23.
DOI:	10.1016/j.cell.2017.07.038
Abstrakt:	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. (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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