DNA damage Flashcards
How do DNA glycosylases find damaged bases?
Scanning the genome for damaged bases Little is known about how DNA glycosylases find damaged bases in the genome. One idea, proposed on the basis of biochemical evidence and theoretical considerations, postulates the association of the glycosylase with undamaged DNA by non-specific interactions, facilitating sliding along the DNA duplex for a certain distance and scanning the sequence for irregular bases (Berg et al. 1981). Considering the structural and functional diversity of DNA glycosylases, however, there are likely to be different translocation mechanisms, variably involving features of tracking, diffusion, and hopping on the DNA (Blainey et al. 2009; Steinacher and Schär 2005; Friedman and Stivers 2010). Recently, an appealing DNA scanning concept was proposed for DNA glycosylases harboring an [4Fe4S] cluster. The underlying observation was that E. coli MutY and Nth change the oxidation state of their iron–sulfur cluster from [4Fe4S]2+ to [4Fe4S]3+ upon contact with DNA, which stabilizes the interaction. Thus, if such DNA glycosylases bind in the vicinity of each other, they might act as electron donors and acceptors for each other, making use of the DNA for charge transfer. This may facilitate the dissociation of one glycosylase upon binding of another by reduction of its [4Fe4S] cluster. If the electron transfer involved is perturbed by a base lesion between the two glycosylases, however, both will stay bound to the DNA, increasing the likelihood of damage detection (Boal et al. 2009). This way, [4Fe4S] clusters may support the search for base damage without a need of scanning the entire DNA sequence.
How many copies of OGG1 per cell
10^5
