Illustration of Cas9 binding to DNA

The Cas9 enzyme (purple; artist's impression) is stymied if it tries to access DNA (blue, white and black strands) that is wound around nucleosome proteins (green). Credit: Janet Iwasa/Univ. Utah

Biological techniques

How DNA fends off a favourite gene-editing tool

Protein–DNA bundles thwart enzymes in the widely used CRISPR–Cas9 gene-editing technology.

The popular genome-editing system CRISPR–Cas9 is a powerful tool for altering DNA sequences. But experiments show that this system cannot edit target sites in DNA wrapped tightly around a protein, which might limit CRISPR’s usefulness.

Many cells store their DNA by winding it around proteins to create structures called nucleosomes. These structures must move or unwind their DNA before enzymes can either copy it or read it to make proteins.

To alter a genome, the CRISPR system cuts a DNA strand at a target site selected by researchers. Dana Carroll at the University of Utah School of Medicine in Salt Lake City and his colleagues found that removing nucleosomes from yeast DNA allowed CRISPR–Cas9 to bind and cut more of its targets. But the CRISPR machinery had difficulty doing so after the researchers inserted DNA mutations that encouraged the formation of nucleosomes.

CRISPR might work well in dividing cells, which unwind their DNA, the authors say. But editing DNA in cells that aren’t dividing might require researchers to remove nucleosomes from CRISPR targets — or to select more-accessible targets.