A new discovery from the Oklahoma Medical Research Foundation could help scientists explain how birth defects start.
When cells divide — part of the process of child development in utero — it's important that the DNA is properly replicated, packaged and divided, said OMRF scientist Susannah Rankin.
In a new paper in the Journal of Biological Chemistry, Rankin describes a pair of nearly identical proteins, called Esco1 and Esco2, with fundamentally different jobs during cell division.
“They're both important in helping orchestrate how chromosomes are packaged,” she said. “If they aren't working correctly, cells can divide with the wrong number of chromosomes. That can lead to developmental disorders, including birth defects, Down syndrome, Roberts syndrome and tumor growth.”
For years, researchers thought the pair of proteins did the same job — anchoring DNA together at the right time during cell division, she said. But the data in the paper suggest they're also vital in correctly packaging the DNA, even before the cell decides to divide.
“Most of us imagine DNA in that classic twisted double helix,” Rankin said. “But in order to fit inside the nucleus of the cell, DNA also has to be wrapped up tightly in coils and loops. And the spots where these proteins ‘weld' loops of genetic material together are incredibly important.”
Imagine an architect stacking the floors of a high-rise building. If the floors shift, even slightly, elevators don't connect, pipes for water and gas lead nowhere and the building will probably fall apart.
By better understanding the basics of how chromosomes are packaged during cell division, Rankin hopes scientists will be able to find ways to predict and reduce developmental problems.
“This is really where biochemistry in human genetics and basic science converge,” she said. “It takes both research into the underpinnings of how cells work and breakthroughs in advanced genetic testing to find and develop new therapeutics.”
The research was funded by grants from the Pew Foundation and the National Center for Research Resources, a part of the National Institutes of Health.
Greg Elwell is a public affairs specialist with OMRF.