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Study reveals instructions for healthy cell division

Scientists have revealed how a key component required for healthy cell division, called the centromere, is passed on from one generation of cells to the next.

Cell division - the centromere is found where identical chromosome strands are tethered together and forms a point of attachment for long fibres, called the mitotic spindle, that pull them apart as the cell divides
The centromere is found where identical chromosome strands are tethered together and forms a point of attachment for long fibres, called the mitotic spindle, that pull them apart as the cell divides.

Discovery of the involvement of critical proteins has revealed how they contribute to the formation and maintenance of a structure - the centromere - that enables cells to divide correctly.

Chromosome segregation

The findings reveal the proteins’ significance in the correct segregation of X-shaped chromosomes - packages of DNA made up of two strands of identical genetic information.

The centromere is found where these identical strands are tethered together and forms a point of attachment for long fibres, called the mitotic spindle, that pull them apart as the cell divides, ensuring genetic information is divided correctly.

Scientists at the University of Edinburgh sought to better understand how the centromere is assembled and targeted to the correct position in specific sections of chromosomes.

Mistakes during chromosome segregation can lead to tumours, developmental disorders such as Downs Syndrome, and miscarriage.

Epigenetic Inheritance

Previous studies have shown that the instructions that create a centromere are not determined by DNA. 

Instead a key protein that acts as the centromere ‘mark’ - called CENP-A - must be located at the right place and replenished in each cell cycle – a process known as epigenetic inheritance.

This study, found that a protein called CAL1 acts to recruit CENP-A and another key centromere protein, CENP-C. 

Further analysis revealed that these three proteins are not only essential but also sufficient to maintain the centromere mark on chromosomes from one cell generation to the next. 

The discovery of these fundamental processes could aid the development of gene therapies by allowing researchers to make artificial chromosomes capable of self-renewing.

The study, funded by the European Research Council and Wellcome, was published in the journal Cell Reports.

 

We were surprised to see that epigenetic inheritance of centromere identity can be kick-started and propagated over time with just three proteins.

Patrick HeunSchool of Biological Sciences

Related Links

Reconstituting Drosophila centromere identity in human cells, Cell Reports 

Patrick Heun Lab