Conventional wisdom dictates that DNA is double-stranded, however around 10 years ago scientists started finding evidence for a four-stranded complex in animal cells. Now for the first time scientists have been able to prove the existence of these complexes in human cells.
What holds DNA together?
Forces called as hydrogen bonds hold the DNA double helix together as long coils. DNA is made up of four alphabets, called bases, and each pair of bases is complementary. When the partner of the base is present on the opposite strand, the two bases are pulled closer together by a force called as a hydrogen bond. Each hydrogen bond is very weak, but together their strength is additive, making DNA a very stable molecule. Hydrogen bonds allow DNA to be zipped and unzipped during replication (formation of new cells) and protein synthesis.
What is the difference between two-stranded and four-stranded DNA?
Four-stranded DNA has a different shape – it is square instead of linear. It also has a different base composition – it is rich in the base Guanine, hence the name G-quadruplexes. Four Guanines from four different sections of the strand interact via a special kind of hydrogen bond to form this square shape.
G-quadruplex DNA is formed by hydrogen bonds between four Guanine bases, forming a tetrad or square shape.
Where is four-stranded DNA found?
Quadruplex DNA is found in nucleus just like double-helix DNA. However the DNA at the tips of chromosomes, called telomeres, is more likely to fold itself into quadruplex-like structures, than other parts of the chromosome. This region is naturally rich in Guanine bases. The natural role of telomeres is to prevent the chromosomes ends from degrading each time DNA in the nucleus replicates during cell division.
So what?
The scientists have shown a clear correlation between the formation of quadruplex DNA and cell replication. They have also shown that regions of the genome involved in regulating cell growth are rich in Guanine bases and therefore potential candidates for G-quadruplex formation. Both of these findings have implications in cancer research.
Cancer is caused when key genes involved in regulating cell growth and division mutate, allowing the cell to replicate in an uncontrolled fashion. A high rate of replication means a high rate of DNA synthesis, and cancer cells are likely to show higher levels of G-quadruplexes than normal cells. Targetting these G-quadruplexes with molecules that stabilise them, thus preventing the cell from completing its cell cycl,e might suggest a route for treatment of these cancers.
Useful links
- Quantitative visualization of DNA G-quadruplex structures in human cells, Biffi et al., Nature Chemistry, Jan 2013 Pdf here: G-quadruplexes
- The discovery of the double-stranded structure of DNA from Cambridge Physics
- The structure and role of double-stranded DNA
- The bonding in G-quadruplexes and their role in telomeres
- Role of oncogenes and tumour supressor genes in cancer
- Video on oncogenes and tumour supressor genes
