摘要：

The second enzyme in the DNA () pathway, apurinic/apyrimidinic (AP) or , hydrolyzes the phosphodiester backbone immediately 5' to an AP site generating a normal 3'-group and an abasic deoxyribose-5-phosphate, which is processed by subsequent enzymes of the pathway. AP sites are the most common form of DNA damage, and the persistence of AP sites in DNA results in a block to , cytotoxic mutations, and genetic instability. Interestingly, /ref-1 is a multifunctional protein that not only is a enzyme, but also functions as a redox factor maintaining factors, such as , , nuclear factor-kappaB, PAX (paired box-containing family of genes), hypoxia inducible factor-lalpha (), -like factor, and , in an active reduced state. /ref-1 has also been implicated in a number of other activities, one of which is the activation of bioreductive drugs requiring reduction for activity. In this report, we present data supporting our findings that another level of posttranslational modification of /ref-1 that clearly affects the activity is the reduction or oxidation of this protein. Furthermore, we show data demonstrating that at least one of the sites involved in this redox regulation is the cysteine amino acid found at position 310, immediately adjacent to the crucial at position 309 in the active site. These findings suggest that the /ref-1 protein may be much more intimately regulated at the posttranslational level than initially imagined.

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