Dr Ali Tavassoli, a Reader in chemical biology at the University of
Southampton, along with his collaborators, Dr Jeremy Blaydes and Professor Tom
Brown, has lead an interdisciplinary study that assembles DNA which is
functional in human cells using click chemistry. A linker has been used to stitch
DNA strands together. Human cells can still read through this DNA correctly
irrespective of the fact that linker used was not found in nature. This finding
has opened doors to the possibility of total chemical synthesis of DNA.
Click chemistry functions like nature to generate substances quickly by
joining small units together. Oligonucleotides were joined together to create
artificial DNA using click chemistry. The usual approaches to assemble DNA
strands comprises of DNA synthesis, PCR
amplification and enzymatic ligation. Click technique has several advantages over
these usual techniques apart from being greatly efficient.
DNA is a strand of nucleotides that
are attached together using phosphodiester bond, with the help of pentose
sugars and phosphate groups. According to Dr Tavassoli, chemists had always
assumed this phosphodiester bond to be essential for DNA functioning in the cell.
However, in recent study using click technique, Modified DNA strands were
stitched together rapidly and efficiently using the copper-catalysed
alkyne-azide cycloaddition reaction. Click-linking DNA leaves behind a
triazole group in the backbone and it was feared that cellular machinery would
be unable to read these unnaturally joined DNA strands. However, the new study
demonstrated error-free transcription in human cells, the first example of a
non-natural DNA linker working correctly in eukaryotic cells.
This discovery not only gives an alternative to enzymatic methods for
DNA assembly, but also suggests that we don't have to stick to the
phosphodiester backbone of the DNA at the site of DNA ligation.
