A look ahead
So, yesterday I finished my life as undergraduate: at least lectures are now over and, to state the obvious, that makes me feel really good.
To conclude the Camptothecin Week, I think it’s finally the time to briefly outline some of the feature of the target of this drug: Topoisomerases.
Not only is this the first time I talk about molecular biology (although somehow indirectly), but this particular enzyme deserve to be mentioned here, since the group where I’m going to work at my graduation thesis, next year, focus their research on this class of enzymes.
Moreover, they have recently got an article about Camptothecin and eukaryotic topoisomerase I published.
Although the use of Camptothecin has to do with the eukaryotic form, the best way to describe the role of this protein is to look at prokaryotes.
In fact, it’s not that complicated to understand the importance of an enzyme which relaxes the strain in a circular DNA...
As such DNA begins to be duplicated, the replication fork moves forward, another part of the circle predictably coils. As a result, as replication goes on, it gets harder for this procedure to continue, facing a tight, positive supercoil.
To relieve such an intolerable strain (or, in other words, yield negative supercoils), topoisomerases are needed: they cut one (type I) or both (type II topoisomerases) strands of the DNA.
This, however, is only half of the story the nick provides a sort of open gate, which allows an another, unchanged strand to pass through, relaxing the overall structure.
There’s a tyrosine in the active site of the enzyme which reacts directly with phosphodiester bonds: so, this intermediate guarantees that most of the energy is conserved and ready to power the last step (the reunion of the strand).
The existence of the intermediate DNA-tyrosine not only has been proved, but it is also where Camptothecin plays its function, stabilizing the adduct so much that the pathways can’t reach the last step.
