Image credit: Darryl Leja, NHGRI (CC BY 2.0)
DNA molecules consist of two separate strands that spiral around each other to form a structure called the double helix. Each strand contains repeating units, with every unit consisting of a phosphate group and a sugar molecule bound to one of four bases. The two strands are held together by bonds between the bases.
When a cell divides, it needs to make a copy of the DNA, so that each new cell will have an exact replica from the old cell. During this process, the helix unwinds and enzymes called polymerases produce new strands (using the old ones as a template). Each strand is copied by adding new bases one at a time. Every time a new base is added, the polymerases must modify their structures several times. If this process becomes faulty, it can lead to various diseases, including cancer.
Scientist often use a technique called X-ray crystallography to study intermediate structures of frozen polymerase crystals as the enzyme constructs DNA. Yet, to fully understand the mechanisms of DNA synthesis all intermediate structures need to be identified.
Now, Chim, Jackson et al. used a particular method for making frozen polymerase crytals by allowing the enzyme to add new bases in liquid form. The reaction was then frozen and X-ray crystallography was used to take images. This modified method captured different steps in the process and detailed how the enzyme adjusts its structure as it moves along the template strand.
The intermediate structures that Chim, Jackson et al. uncovered may help scientists develop new biotechnologies and medicines. Understanding how polymerases modify their form while making DNA copies could lead to better therapies for diseases in which this process has become faulty, like cancer.
