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How cells rebuild after they divide

New research demonstrates how cells rebuild using actin...


When cells divide, they need to rebuild their nucleus and organise their genome. New research from the University of Bristol demonstrates how cells achieve this. Published online in Nature Cell Biology, this is the first evidence that actin polymerisation when small molecules join together to make very long molecules helps reshape the nucleus, reorganising the genome after mitosis or cell division.

In mammals, including humans, the cell nucleus packages and protects the genome. When human cells divide, the nucleus is pulled apart as chromosomes segregate into two pairs. Once chromosome segregation is complete, cells need to re-build their nucleus and organise the newly divided chromosomes into the now two cells - the original cell and its daughter cell. This process is essential for life. On one hand it builds new tissue, while it also is how damaged tissue is repaired. However, the process is so complex as to have been poorly understood in all of its manifestations.

Now, Robert Grosse and his laboratory at the University of Marburg, Germany reveals that transient and highly dynamic F-actin chains quickly form from globular actin found in the nucleus of daughter cells. The conversion of globular actin or G-actin to the linear polymer microfilament called F-actin (filamentous) assists the nucleus in rebuilding. Formation of F-actin chains in the cytoplasm gives shape to the cell and enables cell movement through chain expansion and contraction.

Alice Sherrard co-first author of the study and PhD student with Dr Abderrahmane Kaidi, University of Bristol, developed methods to visualise nuclear structure and genome reorganisation. She found that if F-actin formation is disrupted, the cell fails to expand its' nuclear volume and cannot de-compact the genomic material within. Because of these defects, cells become inefficient in retrieving genetic data encoded in their DNA and divide slower.
"This research highlights the importance of the spatiotemporal control of genome organisation for normal cell function, and we continue to define the principals that regulate these processes and their impact on cancer and degeneration."

Abderrahmane Kaidi PhD, Cancer Biology Specialist, School of Cellular and Molecular Medicine, Biomedical Sciences, University of Bristol, UK.

Abstract
Re-establishment of nuclear structure and chromatin organization after cell division is integral for genome regulation or development and is frequently altered during cancer progression. The mechanisms underlying chromatin expansion in daughter cells remain largely unclear. Here, we describe the transient formation of nuclear actin filaments (F-actin) during mitotic exit. These nuclear F-actin structures assemble in daughter cell nuclei and undergo dynamic reorganization to promote nuclear protrusions and volume expansion throughout early G1 of the cell cycle. Specific inhibition of this nuclear F-actin assembly impaired nuclear expansion and chromatin decondensation after mitosis and during early mouse embryonic development. Biochemical screening for mitotic nuclear F-actin interactors identified the actin-disassembling factor cofilin-1. Optogenetic regulation of cofilin-1 revealed its critical role for controlling timing, turnover and dynamics of F-actin assembly inside daughter cell nuclei. Our findings identify a cell-cycle-specific and spatiotemporally controlled form of nuclear F-actin that reorganizes the mammalian nucleus after mitosis.

Authors: Christian Baarlink, Matthias Plessner, Alice Sherrard, Kohtaro Morita, Shinji Misu, David Virant, Eva-Maria Kleinschnitz, Robert Harniman, Dominic Alibhai, Stefan Baumeister, Kei Miyamoto, Ulrike Endesfelder, Abderrahmane Kaidi & Robert Grosse

This collaborative study is funded by Human Frontiers Science Program, Medical Research Council and Wellcome Trust; and benefited greatly from the Bristol Wolfson Bioimaging (Biomedical Sciences), and the Bristol Electron Microscopy Unit (Chemistry).

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Dec 5, 2017   Fetal Timeline   Maternal Timeline   News   News Archive




Illustration of nuclear F-Actin reshaping cell nucleus and organizing the genome.
Image Credit: Claudia Stocker of Vivid Biology.


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