Possible roles of β-elimination and δ-elimination reactions in the repair of DNA containing AP (apurinic/apyrimidinic) sites in mammalian cells

Abstract

Histones and polyamines nick the phosphodiester bond 3'' to AP (apurinic/apyrimidinic) sites in DNA by inducing a .beta.-elimination reaction, which can be followed by .delta.-elimination. These .beta.- and .delta.-elimination reactions might be important for the repair of AP sites in chromatin DNA in either of two ways. In one pathway, after the phosphodiester bond 5'' to the AP site has been hydrolyzed with an AP endonuclease, the 5''-terminal base-free sugar 5''-phosphate is released by .beta.-elimination. The one-nucleotide gap limited by 3''-OH and 5''-phosphate ends is then closed by DNA polymerase-.beta. and DNA ligase. We have shown in vitro that such a repair is possible. In the other pathway, the nicking 3'' to the AP site by .beta.-elimination occurs first. We have shown that the 3''-terminal base-free sugar so produced cannot be released by the chromatin AP endonuclease from rat liver. But it can be released by .delta.-elimination, leaving a gap limited by 3''-phosphate and 5''-phosphate. After conversion of the 3''-phosphate into a 3''-OH group by the chromatin 3''-phosphatase, there will be the same one-nucleotide gap, limited by 3''-OH and 5''-phosphate, as that formed by the successive actions of the AP endonuclease and the .beta.-elimination catalyst in the first pathway.