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: Every cell in the human body faces a chronic challenge: protecting its DNA. Whenever cells divide, their genetic material must be copied accurately.
But DNA is continuously under attack, and when damage goes unrepaired, it can threaten genome stability and contribute to the progression of disease. Now, a new study led by University of Ottawa Faculty of Medicine researchers reveals how a specialized protein helps cells safeguard their genetic material. Published in Science Advances, the findings also shed light on the progression of a rare inherited skeletal disorder by showing how mutations can interfere with the machinery responsible for DNA repair.
"Our DNA is constantly exposed to damage, so cells rely on specialized proteins not only to repair it, but also to recognize where and when that repair is needed," says Dr. Jean-François Couture, co-corresponding author of the study and full professor in the faculty's Department of Biochemistry, Microbiology and Immunology (BMI). "Our work shows how even subtle changes that interfere with this recognition can compromise DNA repair, threaten genome stability and, ultimately, contribute to disease." The work's first author is Dr.
Hossein Davarinejad, a postdoctoral fellow in Couture's lab and the 2024 recipient of the Polanyi Prize in Physiology and Medicine, an award named after Nobel laureate John Polanyi. Amélie Fradet-Turcotte at Université Laval is the study's co-corresponding author. Inside our cells, DNA is packaged around proteins called histones.
These proteins organize genetic material and help regulate how it is accessed. Different versions of histones, known as variants, carry distinct molecular features that other proteins can recognize. The newly published study shows that chemical changes to a histone variant dubbed H3.1 regulate how it interacts with the TONSL protein (involved in maintaining genome integrity) and that these interactions play an important role in repairing damaged DNA.
The collaborators discovered that these proteins use several molecular binding pockets to recognize histones. Rather than relying on a single point of contact, the pockets work together to interpret multiple chemical signals. The team also found that two of these pockets recognize specific chemical modifications on H3.1: methylation at one position and acetylation at another.
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