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

Publication date: 24 August 2017
Source:Cell, Volume 170, Issue 5
Author(s): Matthias Samwer, Maximilian W.G. Schneider, Rudolf Hoefler, Philipp S. Schmalhorst, Julian G. Jude, Johannes Zuber, Daniel W. Gerlich
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.

Graphical abstract

Teaser

The BAF protein promotes the formation of a single nucleus via its DNA cross-bridging activity during nuclear assembly after mitosis.


from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2gdW3tv
via IFTTT