Point-Mutation Effects on Charge-Transport Properties of DNA

Abstract

There is increasing evidence that DNA can support a considerable degree of charge transport along the strand by hopping of holes from one base to another, and that this charge transport may be relevant to DNA regu ation, damage detection and repair. A surprisingly useful amount of insight can be gained from tne construction of simple tight-binding models of charge transport , which can be investigated using the transfer-matrix method. The data thus obtained indicate a correlation between DNA charge-transport properties and the locations o f cancerous mutation; We review models for DNA charge transport and their extension to include more physically realistic diagonal-hopping terms. In the present paper, we will investigate electronic transport in DNA by (i) introducing what appears to be the most appropriate tight-binding model of DNA and (ii) studying its transport characteristics for a large set of cancer-related genes given by the human genome mutation database. We find that (i) the conductance o f hot spots of caneerous mutations is smaller than that of other sites, (ii) on average the cancerous mufations yield smaller changes of the charge-transport in contrast with noncancerous mutations, (iii) the tendency in (ii) is stronger in the set of highly cancerous mutations with occurrence frequency > 10. These results suggest a possible scenario of how cancerous mutations could circumvent the DNA-damage-repair mechanism and survive to yield carcinogenesis. Our analysis is however only valid in a statistical sense since occasional noncancerous mutations are found to yield weak change of charge-transport. For these, other DNA repair processes should exist so that the DNA-damage repair might not solely uses a charge-transport-based criterion. Still, our results exhibit an intriguing and new correlation between the electronic structure o f DNA hot spots and the damage-repair process..