UV DNA Damage

Exposure to sunlight damages DNA. We understand repair by watching this process in real-time

 

Our genomes are constantly assaulted by enironmental and endogenous damaging agents. Without DNA repair our cells would die or mutate, therefore multiple mechanisms of DNA repair exist to correct damaged DNA. Of these processes we are interested in Nucelotide Excision Repair (NER), this is perhaps the most promiscuous mechanism of repair and is responsible for removing UV-induced lesions. Our studies of DNA repair involve labelling the individual component proteins (shown in the diagram on the left) using quantum dots and watching how they interact with each other and DNA in real time. Our key findings to date include:

 

 

  • UvrA appears to use a 3D search mechanism with no detectable sliding to locate lesions. Our calculations indicate that this is highly inefficient and therefore unlikely to be successful.

  • When incubated with UvrB a UvrAB complex is formed, unlike UvrA alone this complex can diffuse laterally on the DNA once bound. This increases the footprint of the search zone resulting in much more efficient target localisation.

  • UvrB forms a complex with UvrC in the absence of UvrA.

  • The UvrBC complex diffuses on DNA once bound much like UvrAB. We are not sure what the role is for this complex in repair, we postulate that it may have a role in chaperoning the endonuclease activity of UvrC. Keeping UvrC from the DNA would prevent spurious cutting.

 

Research Sponsored by:

BBSRC