Researchers at The Scripps Research Institute have figured out how a macromolecular machine is able to unwind the long and twisted tangles of DNA within a cell's nucleus so that genetic information can be "read" and used to direct the synthesis of proteins, which have many specific functions in the body.
The scientists say that their findings, published in the November 23, 2008 online issue of Nature Structural & Molecular Biology , provide important new insights into this critical DNA unwinding.
"This is a fundamental processes that takes place countless times inside each of our cells every day, but how it happens had not been understood." says the study's lead investigator, Francisco Asturias, Ph.D., associate professor in the Department of Cell Biology at Scripps Research. "The structure we have solved provides important clues into one of the first steps in gene expression regulation."
To accomplish this feat, the scientists used a technique called macromolecular cryo-electron microscopy, in which images of individual molecules preserved at extremely low temperatures are recorded and used to determine the molecule's structure. Using samples from the yeast Saccharomyces cerevisiae, the scientists were able to take thousands of individual pictures of the RSC chromatin remodeling complex—a large and flexible protein machine that unwinds the DNA—in complex with the nucleosome, the basic organizational unit into which DNA strands are wrapped.
The scientists then used mathematics and intensive digital processing to translate what were two-dimensional snapshots of single RSC molecules into a detailed picture of the three-dimensional molecular machine at work.
"Remarkable Unpacking and Repacking"
To understand the complexity of the process, it is important to know that if the DNA in each cell were stretched out, it would be more than three feet long—and given the trillions of cells within a human body, it has been calculated that a single individual's DNA could stretch to cover the distance to the sun and back many times over.
So DNA must be packaged into tidy little chromosomes. The DNA in each gene first assembles into what looks like a string of beads: the string is the DNA and to compact its length, it is wrapped two times around a spool-like bead of histone protein, to form a nucleosome. But there is so much DNA in a single gene that each gene is packed into a necklace of nucleosomes on a DNA string. These beads then become further compressed into twisted ropes that eventually form chromatin, in which DNA is compacted about 10,000 times from its extended length.
What the Scripps Research scientists set out to do is to understand how the RSC complex unwinds DNA from the many histone beads within a gene so that other molecular machines can read the genetic code.