2018Proceedings of the National Academy of SciencesOpen access

Nonenzymatic release of N7-methylguanine channels repair of abasic sites into an AP endonuclease-independent pathway in Arabidopsis

Casimiro Barbado, Dolores Córdoba‐Cañero, Rafael R. Ariza, Teresa Roldán‐Arjona

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Abstract

Significance Abasic (apurinic/apyrimidinic, AP) sites in DNA result from spontaneous and repair-mediated base release. They may be processed by AP endonucleases or AP lyases, but the relative roles of both types of enzymes are poorly understood. Our study reveals that the model plant Arabidopsis uses an AP lyase-dependent pathway to repair AP sites generated by spontaneous loss of N7-methylguanine (N7-meG), a major lesion arising from DNA methylation damage. We further show that the main Arabidopsis AP endonuclease is active on AP sites generated by enzymatic excision of N7-meG, but not on those arising from N7-meG loss. Our findings identify an important role for AP lyase activity in plants and challenge the assumption that spontaneous and repair-generated AP sites have identical biochemical properties.

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Significance Abasic (apurinic/apyrimidinic, AP) sites in DNA result from spontaneous and repair-mediated base release. They may be processed by AP endonucleases or AP lyases, but the relative roles of both types of enzymes are poorly understood. Our study reveals that the model plant Arabidopsis uses an AP lyase-dependent pathway to repair AP sites generated by spontaneous loss of N7-methylguanine (N7-meG), a major lesion arising from DNA methylation damage. We further show that the main Arabidopsis AP endonuclease is active on AP sites generated by enzymatic excision of N7-meG, but not on those arising from N7-meG loss. Our findings identify an important role for AP lyase activity in plants and challenge the assumption that spontaneous and repair-generated AP sites have identical biochemical properties.

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Available abstract

Significance Abasic (apurinic/apyrimidinic, AP) sites in DNA result from spontaneous and repair-mediated base release. They may be processed by AP endonucleases or AP lyases, but the relative roles of both types of enzymes are poorly understood. Our study reveals that the model plant Arabidopsis uses an AP lyase-dependent pathway to repair AP sites generated by spontaneous loss of N7-methylguanine (N7-meG), a major lesion arising from DNA methylation damage. We further show that the main Arabidopsis AP endonuclease is active on AP sites generated by enzymatic excision of N7-meG, but not on those arising from N7-meG loss. Our findings identify an important role for AP lyase activity in plants and challenge the assumption that spontaneous and repair-generated AP sites have identical biochemical properties.

Key concepts: AP site, AP endonuclease, Base excision repair, DNA-(apurinic or apyrimidinic site) lyase, Endonuclease, Arabidopsis, DNA repair, DNA damage

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