DNA has to be carefully packaged and organized in cells so it will both physically fit into the nucleus, and also remain accessible to the cellular machinery that transcribes active genes. Together, compacted DNA and it's associated proteins are known as chromatin, and scientists have long observed that chromatin often sits near an inorganic molecule—a biopolymer polyphosphate (polyP); this association is seen in all domains of life and can influence many cellular processes. In many bacterial cells, polyP and chromatin are usually found together when magnesium is present.
Now scientists have learned more about the relationship between DNA, magnesium, and polyP, and how they come together in a perfect balance. The findings have been reported in Nature Communications.
PolyP and magnesium play a role in many different biological functions. This study has shown that there is an ideal level of magnesium, a so-called Goldilocks zone, in which DNA will wrap around droplets or condensates of polyP and magnesium. This creates a kind of eggshell around the condensate. These wrapped condensates may affect the formation of other condensates, since unwrapped polyP-magnesium condensates (without DNA) will readily fuse together.
This study showed that the condensate fusion rate also depended on the size of the DNA molecule on the condensate. DNA only wrapped around condensates when magnesium levels stay within a certain range, and this can impact the structure, size and function of condensates. These DNA molecules protrude from the surface, like tangles of hair.
Polyp and magnesium condensates can vary in size and shape, and the study noted that these ancient inorganic materials have a remarkable ability to organize DNA. These condensates may also affect the transport of molecules.
“Being molecular detectives, seeing these [magnesium-rich polyP condensates] raised exciting questions for us about the physics and mathematics of the DNA shells and whether they influenced the polyP condensates,” noted co-senior study author Professor Ashok Deniz, PhD of The Scripps Research Institute.
“Although we think of cellular interfaces as boundaries, they also create a new landscape by providing a surface for molecules to organize,” said co-senior study author Associate Professor Lisa Racki, PhD, also of Scripps. “DNA may not actually be a tangled mess at the surface and is instead organized by these condensates.”
The interaction between DNA and condensates could alter DNA packaging, which may have downstream impacts on gene expression or cell function. The researchers want to know more about these questions.
"We’re excited by the prospects of leveraging these discoveries to develop new tools for cellular control—potentially simpler, more cost-effective approaches to manage biomatter for biomedicine,” added Deniz.
Sources: The Scripps Research Institute, Nature Communications
