THE vast complex of proteins that copies our chromosomes seems to play a
direct role in preserving the identity of cells, says Bruce Stillman, director
of the Cold Spring Harbor Laboratory on Long Island, New York.
When a cell divides to create two daughters, its DNA must be replicated. But
perhaps more remarkably, the way in which the DNA is packaged with proteins to
form chromatin must also be reproduced. A cell鈥檚 identity鈥攚hether it鈥檚 a
skin, gut or some other type of cell鈥攄epends on which genes are active.
Inactive or 鈥渟ilenced鈥� genes often have chemical markers on their DNA or on
packaging proteins. So, for a daughter to be the same as its mother, it too must
carry these markers.
Exactly how chromatin is copied is unclear. But Stillman and his colleagues
unexpectedly discovered a piece of the puzzle while studying a protein called
PCNA, a barrel-shaped molecule 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 is thought to add silencing proteins to genes
(Cell, vol 96, p 575).
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So it seems the same complex of proteins that copies DNA also transfers at
least some of the special markers to the new chromosome. To test the idea, the
researchers found mutant yeasts in which PCNA has a weakened bond to CAF-1. The
yeasts were also genetically engineered to turn red if a certain gene was
silenced. Sure enough, the mutants grew into colonies with white and red
sectors, showing that the gene was flipping between its silenced and active
states. The chromatin was no longer being faithfully inherited.
Stillman reckons that PCNA recruits chromatin factors lay down the markers,
just as the DNA is being replicated. 鈥淚 think this shows the replication field
hasn鈥檛 died,鈥� says Stillman. 鈥淭here are still many things left to be
诲颈蝉肠辞惫别谤别诲.鈥�