This protein, called CENP-A, keeps a "molecular memory" of the centromere, ensuring its inheritance. Previous studies, by Lars and other research groups, had shown that, while cells duplicate their DNA before mitosis, duplication of the centromere, led by the CENP-A protein, takes place only after mitosis (during a 'gap' phase called G1). What triggers its duplication and how accuracy is ensured remained unknown.
Lars and his team now show that the very same machinery that is controlling the well-known process of DNA duplication is also controlling CENP-A duplication. This machinery, that includes the so-called cyclin-dependent kinases (Cdks) acts like a molecular clock driving the different steps of the cell cycle forward, one after the other. When Cdks are highly active (just before mitosis) DNA duplicates while duplication of CENP-A is inhibited. Conversely, when they are inactive (after mitosis), CENP-A is duplicated but at that point DNA duplication is inhibited. In other words, when DNA duplicates at midnight, Cdks make sure that the centromere is copied only at noon.
The IGC researchers came to this elegant model by painstainkingly inhibiting Cdk activity in human and chicken cells at set times. When doing so, they could fool the cells into making new centromeres even while the cells were in the middle of duplicating their DNA. "Its like a cell with a jetlag", says Lars Jansen.
Lars puts their findings into context "What we've uncovered is a very simple, neat mechanism whereby the cell couples DNA duplication, cell division and centromere assembly. By using the same machinery (Cdks) for all these steps but in opposite ways, the cell makes sure that the right number of copies of both genes and centromeres are made by allowing each the appropriate time. Keeping these critical processes separate in time might be important to avoid errors in either one. Understanding these general pr
|Contact: Ana Godinho|
Instituto Gulbenkian de Ciencia