A range of proteins implicated in interactions with nucleic acids have been found to contain small structural domains that are organized around bound zinc ions. The most well characterized of these domains are the Cys2His2 """"""""zinc finger"""""""" domains. These domains occur in up to 1000 human gene products and mutations within these domains have been implicated in cancer development. Through structural and other studies, it has become possible to design rationally site-specific DNA binding proteins based on these domains. Additional studies will be performed to test and extend these design capabilities. In addition, some members of this protein family have been implicated in zinc sensitive regulatory processes. Metal binding studies will be performed to test the role of the zinc finger domains in zinc sensing. Other proteins that appear to be members of this family are involved in RNA splicing. Metal binding and structural studies will be initiated to probe the role of interactions with DNA has recently been discovered in proteins expressed in the nervous system. Metal binding and structural studies will be performed to elucidate the properties the properties of these domains that enable them to interact with DNA. Taken together, these studies will extend our knowledge of the structural and functional roles of zinc binding domains in nucleic acid and gene regulatory proteins.
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| Shi, Y; Berg, J M (1996) DNA unwinding induced by zinc finger protein binding. Biochemistry 35:3845-8 |
| Shi, Y; Berg, J M (1995) Specific DNA-RNA hybrid binding by zinc finger proteins. Science 268:282-4 |
