Identification of a new mechanism which is essential for proper DNA segregation

Anne Pacquelet, a researcher in Grégoire Michaux’s team, and her colleagues from the IGDR, Perrine Uhart and Jean-Pierre Tassan, identified a new mechanism which controls the position of the cytokinetic furrow and plays a crucial role to ensure proper DNA segregation during cell division. This work is published in The Journal of Cell Biology (vol. 210, no.7, September 2015).

DNA segregation, a crucial step of cell division

As a cell divides, its genetic material needs to be equally segregated between the two daughter-cells. This segregation of the genetic material is a crucial step of cell division. Improper DNA partitioning indeed results in aneuploidy, which can in particular lead to cancer cell formation. Several mechanisms ensure proper DNA segregation.

First, the mitotic spindle partitions the chromosomes in two equal sets. The mitotic spindle then controls the formation of the cytokinetic furrow which cleaves the mother cell between the two sets of chromosomes. Myosin, a cytoskeleton protein, is also able to induce the formation of a cytokinetic furrow, independently of the mitotic spindle.

However, in certain cells, myosin and the mitotic spindle are localized to opposite sides of the cell. In those cells, does the furrow position result from an equilibrium between the signals coming from the mitotic spindle and from myosin? Do these signals need to be regulated so that the furrow equally partitions DNA? These are the questions that Anne Pacquelet and her colleagues from the IGDR tried to answer.

A new mechanism regulating furrow position

To study the mechanisms underlying cell division, the researchers used the one-cell embryo of the worm C. elegans, a big cell which allows to easily following the different steps of cell division. In this cell, myosin accumulates at the anterior at the beginning of division whereas the mitotic spindle is localized towards the posterior.

Through a series of genetic experiments, they uncovered that furrow and spindle positions coincide thanks to several proteins, anillin and the kinases PAR-4/LKB1 and PIG-1/MELK, which restrict myosin accumulation when the furrow starts to form. In the absence of anillin and PAR-4/LKB1 or PIG-1/MELK, myosin accumulation increases and lasts longer: this results in a strong shift of the cytokinetic furrow which can then not cleave through the two sets of chromosomes.

This work thus reveals the importance of a new mechanism regulating myosin activity during cell division. This mechanism is essential to coordinate furrow and spindle positions, thereby allowing the proper partitioning of the genetic material.

This study opens new avenues on the possible causes of DNA segregation defects observed in human cells and on the role of the PIG-1/MELK kinase, which is known to be overexpressed in many human tumors. 

More informations

>> Abstract of the article "PAR-4 and anillin regulate myosin to coordinate spindle and furrow position during asymmetric division" 



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