This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Two new studies from Johns Hopkins University are providing scientists with an unprecedented view of how human cells repair one of the most dangerous forms of genetic damage: a break that severs both strands of the DNA double helix. Published back-to-back in Nature Communications, the studies examine different stages of a repair process called "non-homologous end joining," or NHEJ.
Together, the findings show how cells gain access to damaged DNA packaged inside chromatin and assemble a versatile collection of molecular tools to prepare and reconnect its broken ends. The research could ultimately contribute to better cancer treatments and more predictable gene-editing techniques. Its immediate importance, however, lies in improving scientists' fundamental understanding of a repair system that protects the human genome every day.
DNA carries the biological instructions cells need to function. Damage to one side of the DNA molecule is generally manageable, but a double-strand break cuts completely through its twisted-ladder structure. If the break is not repaired—or is repaired incorrectly—the cell can die or acquire mutations and rearrangements that contribute to diseases such as cancer.
NHEJ is one of the principal systems human cells use to address this emergency. The process identifies the two broken ends, holds them together, prepares them for reconnection and seals the break. "These are among the very first studies to view DNA as it actually appears in a cell—wrapped around histones and with broken ends that cannot be stitched together easily," said He, who has appointments in the university's departments of biophysics and biology.
"This could help us design the next generation of cancer therapies." Weifeng Lu, a doctoral student in He's laboratory at Johns Hopkins, is first author of the chromatin study. Alex Vogt of Northwestern University is first author of the end-processing study and a co-author of both. The work was carried out with collaborators at the University of Calgary, the National Institute of Environmental Health Sciences and the University of New Mexico.
The first study addresses a longstanding question about how this repair machinery operates inside the crowded environment of a cell. DNA does not ordinarily float freely in the cell nucleus. It is wrapped around proteins called histones, forming structures known as nucleosomes.
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