Missing link in cell division discovered

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.

"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.

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