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The protein machine that copies our chromosomes also plays a direct role in preserving the developmental state of cells, suggests a new experiment presented by Bruce StillmanBruce Stillman, director of the Cold Spring Harbor Laboratory on Long Island, New York.Fig. 1Bruce Stillman How do the daughters of a skin cell know that they too are skin cells?View Large Image | Download PowerPoint SlideIn many cases when a cell divides, it gives rise to two identical daughter cells. This means the DNA must be replicated. But perhaps more remarkably, it means the protein structure that packages the DNA, called chromatin, must also be reproduced for each gene to remain active or inactive as it was in the mother cell. For instance, inactive or silenced genes often have special marks on their DNA or chromatin that must be re-established with each cell division.Exactly how this chromosome structure is copied from generation to generation is unclear. But Stillman and his colleagues unexpectedly discovered a piece of the puzzle while they were studying a replication protein called PCNA, a barrel shaped molecule in all higher cells that clamps on to DNA and opens it up as it is copied. They found that PCNA interacts with another protein called chromatin assembly factor-1 (CAF-1) which was thought to recruit silencing proteins to genes (Cell, vol. 96, p. 575).This suggested that the same complex of proteins that copies the DNA also transfers at least some of the special marks to the new chromosome as well. To test the idea, the researchers found mutants of the yeast Saccharomyces cerevisiae in which PCNA has a weakened bond to CAF-1. The yeast were also genetically engineered to turn red if a certain gene was being silenced. Sure enough, in mutant cells the yeast grew as colonies with white and red sectors, showing that the gene was flipping back and forth from its silenced state to an active state, and that the chromatin state was no longer faithfully inherited.Stillman suggests that PCNA recruits chromatin factors just as the DNA is being replicated. However, what it is also interesting is that copies of PCNA get left behind as the replication complex advances down the chromosome, so it could serve as a long-term anchor for silencing proteins. “I think this shows the replication field hasn't died,” says Stillman. “There are still many things left to be discovered.”