Nobel prize for elucidating the molecular structure of dna
Another enzyme, endonuclease, then cuts the phosphodiester bonds around the remaining nucleotide to remove it before DNA polymerase is pasted into the empty site to produce a new base scaffold.‘It’s the same principle as a dentist has when he fixes a hole,’ explains Lindahl.‘He cleans up a little bit around the hole to get a clean area and then fills it in again.’‘Your DNA is maintained in this very stable state because there is this kind of to-and-fro – there is the introduction of DNA damage and there is the recognition and removal of DNA damage,’ says West.Over the next two decades, and following a move to Cancer Research UK’s Clare Hall Laboratories as the site’s new director in 1986, Lindahl and his colleagues meticulously mapped out this repair mechanism, base excision repair (BER), reconstituting it in human cells., uracil–DNA glycosylase in human cells locates the uracil base by bending the DNA backbone for ease of access.The enyzme’s intercalation group flips the nucleotide base out of the helix before severing the glycosidic bond to remove the uracil.
But it wasn’t initially a surprise to many chemists at the time.The physical structures that surround us all exude a sense of stability – be it the homes we live in or the roads that we travel on.They are built with the best of intentions to stand the test of time, but are all vulnerable to the inevitable threats of aging and decay.‘That’s what Tomas really realised before anyone else did.’During this time, Lindahl, along with his colleague Richard Wood, now based at the University of Texas MD Anderson Cancer Center in the US, was also looking at other repair pathways, activated in response to external damage from UV radiation.
‘Tomas knew that I was interested in UV irradiation effects and he was particularly interested in nucleotide excision repair (NER), getting a system working to study the biochemistry of NER in human cells,’ explains Wood.
For Lindahl, this seemed puzzling.‘In the Watson and Crick days, they discovered the double helix and that there’s this beautiful molecule that replicates faithfully – well, you know, it doesn’t,’ says Stephen West, Lindahl’s former colleague and now a group leader at the Francis Crick Institute, UK.