Cells from a bone cancer caused by a histone mutation are brown if they contain the mutation (left). Purple cells are intact, without the mutation (right).
Credit: Peter W. Lewis
(Science Daily) – A single defect in a gene that codes for a histone – a “spool” that wraps idle DNA – is linked to pediatric cancers in a study published in the journal Science.
“Unlike most cancers that require multiple hits, we found that this particular mutation can form a tumor all by itself,” says Peter W. Lewis, an assistant professor of biomolecular chemistry in the School of Medicine and Public Health at the University of Wisconsin-Madison.
Histones derive their pattern from the same genome that they help to pack up and organize. “A histone’s day job is compacting the genome,” says Lewis. “The histone takes six feet of DNA and packs it in something that is a few microns in diameter.”
Lewis started exploring histone mutations long before arriving at UW-Madison’s Wisconsin Institute for Discovery in 2013. In a publication that year, he and colleagues discovered the mechanism for a histone mutation linked to a fatal brain tumor called DIPG.
Because the DIPG mutation always changed the same amino acid in the same location in the histone gene, Lewis knew something was special about it.
Histones play a role in the “Rube Goldberg” cascade that activates or silences genes. During these processes, a histone is studded with certain chemical groups that attract proteins that, in turn, initiate further events.
The eventual result may be protein formation, another process that uses DNA, or a mechanism that does the reverse and silences the DNA.