In the present era of multimedia boom, a typical video image is not expected to excite anyone.
But a video clip shot by biochemist Desirazu Rao at the Indian Institute of Science, Bangalore and his colleagues in the UK and Japan has stirred the scientific community. Simply because, it is the world’s first real time video image of a DNA-enzyme interaction. An integral part of any living cell, DNA and enzymes are so tiny that they are not only invisible to naked eyes, but most ordinary microscopes cannot even spot them.
Using a special instrument called atomic force microscope (AFM), the team for the first time has been able to film, in real time, the nano-scale interaction of an enzyme and a DNA. An AFM is a very high resolution instrument capable of “seeing” atomic level interactions. “We can actually see how the enzyme molecule is moving along the DNA in real time. It’s just like a movie, which enables us to see things moving on a nano-scale,” an excited Dr Rao told Deccan Herald.
Model to study
The footage shows a bacterial restriction enzyme from Ecoli attaching itself to the DNA of a phage virus to break the DNA before the virus has the chance to infect the bacterium.
It can provide a model for understanding other DNA-enzyme interactions.
“Standard technology for filming on this scale can produce one image frame every eight minutes. But our new technology allows one frame per 500 — or fewer, milliseconds,” explained Dr Robert Henderson, the team leader at the University of Cambridge.
The advancement was possible because of a breakthrough in the AFM technology leading to the development of better AFM machine. Worldwide there are only three such machines and the one used in this case is in the Kyoto University in Japan, said Dr Rao.
Till now, the scientists analysed indirect evidences to make assumptions on how proteins and DNA interact. But this breakthrough opens up a new window to better understand a fundamental biological process, he added. “To be able see these nano-mechanisms as they are really happening is incredibly exciting. We can actually see the enzyme ‘threading’ through a loop in the virus’s DNA in order to lock on to and break it, a process known as DNA cleavage,” explained Dr Henderson.
Therapeutic application
The research has been published in the Proceedings of the National Academy of Sciences (PNAS).
Asked about the implications, Dr Rao said besides fundamental biology, there may be long term therapeutic application in cancer research.
“The video helps us understand how enzymes recognise which bit of a DNA strand to latch onto, which is important in understanding how proteins repair damaged DNA. In the long term, this could help in the search for cancer treatments, as cancer sometimes occurs where DNA is damaged but enzymes do not behave correctly in order to repair it,” said Dr Henderson.