One consequence is especially important: the twist in the structure creates a tortional strain: the two hexamers load with an inherent tension that makes them something like a coiled spring. “The two barrel-shaped hexamers are poised in such a manner that they are ready to untwist the double helix when activated.” “The new images show that once loaded into the double hexamer-or DH, as we call the head-to-head helicases-the double helix takes a zig-zagging path through the central channel, which is sort of kinked,” the authors explain. Based on that new knowledge, insight into how the two DNA strands separate, long a mystery, is beginning to be uncovered. The question answered by the new structure is how the double helix is situated within the channel they form, and how DNA interacts with the surrounding structure. Christian Speck, Professor of Genome Biochemistry and Molecular Biology at Imperial College in London.Ī great deal of past effort has revealed how ORC assembles and finds replication “start sites.” The new research concerns what happens after the initial recognition of the start sites and how the DNA helix is unwound.Īs vividly shown in the new cryo-EM “pictures,” the twin barrel-shaped helicase enzymes that surround the double helix look like symmetrical insects or, perhaps, twin spacecraft docked head to head. The feat was made possible by a new cyro-electron microscopy (cryo-EM) facility at the Van Andel Research Institute, home of one of the lead investigators, Dr. The configuration, a part of what biologists call the pre-replicative complex (pre-RC), has never been successfully imaged in this configuration before. In new research, insight into how the two stands of the double helix separate in the earliest stages of replication is becoming clear.Ī longstanding collaboration by researchers in London, Grand Rapids, Michigan and Cold Spring Harbor Laboratory (CSHL) in New York reports the atomic-level structure of twin helicase enzymes loaded head to head, with the DNA double helix visible in the circular channel that runs though both helicases. A major unsolved part of the puzzle is understanding how the entire process of copying the genome begins. The journey of investigators is not yet done, however. Cancer and other diseases can result when the process goes awry.įiguring out how replication works at the level of individual molecules and atoms is one of the great achievements of modern science. Within daunting tolerances, each new cell must have a genome identical to that of the cell that gave birth to it. These cells alone contain enough DNA to wrap around the earth’s equator 25 times. In our bone marrow alone, half a billion new cells are born every minute.
If unwound, the double helix crammed into each of our cells would measure 6 feet in length. In humans, the task boggles the imagination. Every time a nucleated cell commits to becoming two cells, every “letter” of its genome must be replicated once and only once. New research provides insight into how the two stands of the double helix separate in the earliest stages of replication.Ĭold Spring Harbor, NY - Life would be impossible if the DNA in dividing cells were replicated with anything less than near-perfect precision.
Center for Humanities & History of Modern Biologyįiguring out how DNA replication works at the level of individual molecules and atoms is one of science's great achievements, and the work is not yet done.Business Development & Technology Transfer.Office of Diversity, Equity, & Inclusion.How one family secured the future of a laboratory.