In a study published today in Molecular Cell, University of Copenhagen researchers show that the protein DNAJC9 has an important role in safeguarding histones and thereby chromatin.
"Until now researchers have assumed that histone chaperones only act to passively shield histones. We have found out that DNAJC9 actively engages the cellular protein folding machinery, which means it actively recruits enzymes and molecular chaperones to redeploy histones that have been trapped," says Colin Hammond, who led the study.
Once released from their trapped condition, histones can re-engage histone chaperones like MCM2 and be assembled into nucleosomes to organize chromatin. When the protein DNAJC9 is mutated to lose its ability to recruit the protein folding machinery, the histones stay trapped and are thereby lost for proper chromatin deposition.
"This means that traditional histone chaperones cannot fully protect histone proteins from spurious interactions. Rather, the cell is dependent on the combined action of molecular chaperones and histone chaperones to safeguard these fundamentally important proteins during their dynamic lives," Hammond explains.
DNAJC9 is an essential protein in many cancer cell types and the levels of the protein correlate with the rates at which cancer cells proliferate. Chromatin in cancer cells may be more reliant on DNAJC9 compared to regular cells, and if this is the case DNAJC9 could be a target for the development of future cancer treatments.
"Although it's still early days, we hope this fundamental advance in our understanding of DNAJC9 biology helps to pinpoint a function essential for cancer cell viability with therapeutic potential," Hammond adds.