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Immune cells' genetic 'jam session' is controlled by cell division machinery

If a dividing cell's activity is a pop song, then the same process in an immune cell is an extended-play dance remix. The basics of cell division are the same in both, but there's a heck of a lot more going on in immune cells, Johns Hopkins scientists have discovered.

All dividing cells have to faithfully copy their DNA so that both new cells get the same information, and immune cells are no exception. But only immune cells must do some genetic rearranging -- a genetic "jam session" -- so they can make the endless variety of antibodies needed to fight infections and foreign proteins in general. If this recombination happens at the wrong time or interrupts the wrong genes, lymphoma, a cancer of tissues that make immune cells, may result.

Although the jam session itself -- the actual rearrangement of particular genes -- is well- studied and has an official name, V(D)J recombination, no one had ever tied its beginning or end to the process of cell division.

Writing in the June 10 issue of Molecular Cell, researchers from Johns Hopkins report that the band leader that normally launches the DNA-copying machinery to start cell division also brings the jam session to a close, intricately connecting the two processes.

"V(D)J recombination essentially breaks, cuts out and reattaches DNA, so it uses cell's normal DNA repairing machinery, which just happens to be already working overtime as the cell prepares to copy its DNA," says Stephen Desiderio, M.D., Ph.D., professor of molecular biology and genetics in Johns Hopkins' Institute for Basic Biomedical Sciences, which he directs. "Our guess is that the cell uses the same protein to start DNA copying and end recombination in order to prevent breaks from happening at a time when a repair can't be made."

Desiderio's team a decade earlier discovered that a protein called RAG2, which helps break genes for recombination, ebbs and flows with the steps of cell division. It reaches peak level
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
10-Jun-2005


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