Functioning of the biochemical mechanism in the replication of the genetic code
A team of researchers coordinated by Marco De Vivo, head of the Molecular Modelling and Drug Discovery laboratory of the Italian Institute of Technology in collaboration with the Forschungszentrum supercomputing centre in Germany, and with support by AIRC, has published a study on SAM, the biochemical mechanism for the replication of DNA and RNA information.
The paper, with PhD student Vito Genna as first author, was published in the Journal of American Chemical Society (JACS) in collaboration with Pietro Vidossich, Emiliano Ippoliti and Paolo Carloni from the Forschungszentrum supercomputing centre in Germany, and support by AIRC.
SAM, “Self-Activated Mechanism”, is the key biochemical mechanism for DNA and RNA polymerization inside cells, and was revealed by computer simulations which managed to describe, for the first time, the perfect synchronicity between chemical reactions and the mechanical phases involved.
In any forms of life, DNA, the nucleic acid containing gene information necessary for the correct transmission of gene information from a parent cell to daughter cells, replicates thousands of times every day.
During genetic replication, the information is maintained unaltered by an enzyme called Polymerase, which allows for replication and transcription of new DNA and RNA molecules starting from DNA and RNA mold molecules, by using a substrate of simple nucleotides present in solution to associate them in the new filament being built.
SAM consists of two key steps: incorporation and activation of a DNA nucleotide and DNA translocation before addition of the next nucleotide. SAM connects these two key steps with sequences of biochemical reactions which self-activate, in a continuous fashion, allowing an efficient extension of the DNA or RNA filament.
The knowledge of these biochemical reaction may pave the way to new scenarios in several science areas, from design of new anticancer drugs able to block SAM in cancer cells, to the design of engineered proteins capable of exploiting SAM for industrial purposes; or even to understand XNAs, the molecular bases needed to develop forms of artificial genetic code, synthetic alternatives to natural genetic material having an immense therapeutic potential.