RT Journal Article T1 Nonenzymatic release of N7-methylguanine channels repair of abasic sites into an AP endonuclease-independent pathway in Arabidopsis. A1 Barbado, Casimiro A1 Cordoba-Cañero, Dolores A1 Ariza, Rafael R A1 Roldan-Arjona, Teresa K1 AP endonucleases K1 AP lyases K1 N7-methylguanine K1 Abasic sites K1 Base excision repair AB Abasic (apurinic/apyrimidinic, AP) sites in DNA arise from spontaneous base loss or by enzymatic removal during base excision repair. It is commonly accepted that both classes of AP site have analogous biochemical properties and are equivalent substrates for AP endonucleases and AP lyases, although the relative roles of these two types of enzymes are not well understood. We provide here genetic and biochemical evidence that, in Arabidopsis, AP sites generated by spontaneous loss of N7-methylguanine (N7-meG) are exclusively repaired through an AP endonuclease-independent pathway initiated by FPG, a bifunctional DNA glycosylase with AP lyase activity. Abasic site incision catalyzed by FPG generates a single-nucleotide gap with a 3'-phosphate terminus that is processed by the DNA 3'-phosphatase ZDP before repair is completed. We further show that the major AP endonuclease in Arabidopsis (ARP) incises AP sites generated by enzymatic N7-meG excision but, unexpectedly, not those resulting from spontaneous N7-meG loss. These findings, which reveal previously undetected differences between products of enzymatic and nonenzymatic base release, may shed light on the evolution and biological roles of AP endonucleases and AP lyases. PB National Academy of Sciences YR 2018 FD 2018-01-16 LK http://hdl.handle.net/10668/12021 UL http://hdl.handle.net/10668/12021 LA en NO Barbado C, Córdoba-Cañero D, Ariza RR, Roldán-Arjona T. Nonenzymatic release of N7-methylguanine channels repair of abasic sites into an AP endonuclease-independent pathway in Arabidopsis. Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):E916-E924 NO We thank S. D. Kathe and S. S. Wallace (Universityof Vermont) for the kind gift of Arabidopsis FPG cDNA, Ana M. Maldonadoand Jesús V. Jorrín (University of Córdoba) for generously sharing plantgrowing facilities, and Jara Teresa Parrilla-Doblas (University of Córdoba) for assistance with FPG purification. This study was supported by the Spanish Ministry of Economy, Industry and Competitivity and the European Regional Development Fund under Grant BFU2016-80728-P and by the Junta de Andalucía and the European Regional Development Fund under Grant P11-CVI-7576. C.B. was the recipient of a PhD FPI (Formación de Personal Investigador) Fellowship from the Junta de Andalucía, Spain. DS RISalud RD Apr 6, 2025