Missing link in cell division discovered

18 January 2013

Cell division, where cells and their DNA replicate and divide, is essential to life - but can cause cancer if it goes awry. Now, scientists at Cancer Research UK's London Research Institute (now part of the Francis Crick Institute)  have found the missing puzzle piece that explains how this process happens correctly.

They discovered that a protein complex called centralspindlin connects the cell's skeleton to the cell envelope - its outside layer - so that the final cut partitions the replicated DNA to the two new emerging cells.

Mark Petronczki explained: "During cell division, two events have to be tightly coordinated - the partitioning of the DNA (chromosomes) and the splitting of the cell envelope and, consequently, the entire cell.

Dividing human cell just before the final cut of cytokinesis.

Dividing human cell just before the final cut of cytokinesis. Centralspindlin marks the center of the mitotic spindle and connects the cell envelope to microtubules that make up the spindle. Centralspindlin is coloured red, the mitotic spindle is black and the chromosomes are blue.
© Mark Petronczki

"After a cell's DNA has been replicated, the two sets of chromosomes are pulled to opposite ends of the dividing mother cell - this is known as chromosome segregation. Then the cell is split by a purse string-like constriction, which acts like a tightening belt around the middle of the cell envelope, between the two copies of duplicated chromosomes. This is followed by the final cut, called cytokinesis.

"If chromosome segregation and cytokinesis are not coordinated properly, cell division can generate daughter cells that inherit the wrong number of chromosomes. This can promote the initiation and progression of cancer."

 

 

Animal cells use an internal skeleton structure called the mitotic spindle to segregate the two sets of chromosomes and to define where the cell envelope needs to split.

But Dr Petronczki and his team are the first to explain how the mitotic spindle is connected to the cell envelope during this crucial process. They showed that a protein machine called centralspindlin acts as an anchor by connecting the mitotic spindle and the cell envelope.

"Without this link, the mitotic spindle is unable to hold on to the cell envelope for the final cut in cytokinesis, which means that cell division fails," Dr Petronczki added.

"As a result, the cell inherits two sets of chromosomes - this leads to further genetic damage and can promote the development of tumours."

The article, Centralspindlin links the mitotic spindle to the plasma membrane during cytokinesis, was featured on the front page of Nature.

  • Cell division is necessary for human life but can cause cancer if it goes wrong. Understanding exactly how it happens is essential for research into cancer mechanisms, and ways to prevent the development and progression of this disease.
  • There are three steps in cell division. First the DNA in the cell (made up of chromosomes) must be replicated. Next these chromosomes must be separated so each new cell gets one full copy. Finally, the cell is pinched in the middle and cut in two, with two whole new cells formed.
  • Researchers have now explained how this final step of cell division is made possible, after discovering a critical link between the cell's skeleton and the cell envelope.