In their work, Di Talia and Cross studied a phase of the cell cycle known as G1, during which cells determine whether they are healthy enough to enter another grueling phase of division. G1 is considered critical because mistakes in this process can lead to cancer.

Di Talia and Cross, with colleagues Bruce Futcher and Hongyin Wang at SUNY Stony Brook, found that daughter cells, which normally have Ace2 and Ash1, interpret their size as 20 percent smaller than their birth twin. The researchers show that, without these proteins, daughter cells begin dividing as if they were mother cells, even at a size that would normally be deemed too small. When Ace2 and Ash1 were genetically manipulated to localize into mothers as well, the opposite happened: they unnecessarily continued to grow and began dividing as if they were daughters.

This critical finding showed that the direct target of these two proteins is a gene called CLN3, which scientists have long suspected is the ultimate green light for cells to start dividing. The reason daughter cells spend a longer time preparing for cell division is because both Ace2 and Ash1 lower the expression of CLN3. To make sure daughter cells do not start dividing before they are ready, and as backup, Ace2 also turns on production of Ash1.

"This work builds on our previous findings very nicely," says Di Talia. "That CLN3 is the central regulator of this cell cycle phase and that it is controlled very precisely shows that even small changes can result in big differences."

Source: Rockefeller University