Ionizing radiation introduces a wide variety of chemically diverse products into cellular DNA. In mammalian cells, the biological effects of such DNA damage include cell death, mutation and neoplastic transformation. One of these DNA lesions, the apurinic/apyrimidinic (AP) site, is one of the most frequently encountered lesions with which a cell is confronted. In addition to being produced by radiation, AP sites can be generated by normal cellular processes, by various chemicals and as intermediates in DNA repair processes. As with other radiation-induced DNA damages, AP sites are toxic and mutagenic lesions in the cell. Utilizing an electrophoretic assay, we have recently identified and isolated an apurinic DNA binding factor, ABF-a, present in the nuclei of mouse and human cells. We have also recently isolated two distinct human cDNAs that encode proteins (ABF-b and ABF-c) which preferentially bind depurinated DNA. The overall goals of this project are to characterize the three human DNA damage binding proteins, ABF-a, ABF-b, and ABF-c and determine their roles in the repair of DNA damaged by radiation and other agents in human cells. The approaches to be taken in this project involve utilizing a variety of biochemical, molecular biological and genetic methodologies to provide direct information with regard to the nature and expression of ABF-a, ABF-b, and ABF-c in human and mouse cells. The results from these studies should provide new insights into the nature and functioning of the components involved in the mammalian cellular response to radiation-induced DNA damage. An understanding of DNA repair pathways in mammalian cells, particularly those involving the reversal of radiation-induced damages, is directly relevant to understanding the biological consequences of radiation exposure in humans.
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