Apurinic/apyrimidinic (AP) site recognition by the 5 '-dRP/AP lyase in poly(ADP-ribose) polymerase-1 (PARP-1)

作者：Khodyreva S N; Prasad R; Ilina E S; Sukhanova M V; Kutuzov M M; Liu Y; Hou E W; Wilson S H; Lavrik O I^*

来源：Proceedings of the National Academy of Sciences, 2010, 107(51): 22090-22095.

DOI：10.1073/pnas.1009182107

• Schiff base
• apurinic/apyrimidinic site-binding protein

The capacity of human poly(ADP-ribose) polymerase-1 (PARP-1) to interact with intact apurinic/apyrimidinic (AP) sites in DNA has been demonstrated. In cell extracts, sodium borohydride reduction of the PARP-1/AP site DNA complex resulted in covalent cross-linking of PARP-1 to DNA; the identity of cross-linked PARP-1 was confirmed by mass spectrometry. Using purified human PARP-1, the specificity of PARP-1 binding to AP site-containing DNA was confirmed in competition binding experiments. PARP-1 was only weakly activated to conduct poly(ADP-ribose) synthesis upon binding to AP site-containing DNA, but was strongly activated for poly (ADP-ribose) synthesis upon strand incision by AP endonuclease 1 (APE1). By virtue of its binding to AP sites, PARP-1 could be poised for its role in base excision repair, pending DNA strand incision by APE1 or the 5'-dRP/AP lyase activity in PARP-1.

• 出版日期2010-12-21