Human APE2 and TREX2 Repair 3′-DNA–Peptide Cross-links Derived from Abasic Sites

Histones react with one of the most abundant endogenous DNA lesions, the apurinic/apyrimidinic (abasic, AP) site, to form reversible but long-lived Schiff base DNA-protein cross-links at 3'-DNA termini (3'-histone-DPCs). These DPCs need to be repaired, because 3'-hydroxyl groups are required for DNA repair synthesis and strand ligation. We previously identified three human enzymes, including tyrosyl-DNA phosphodiesterase 1, AP endonuclease 1 (APE1), and three-prime repair exonuclease 1 (TREX1), that can repair chemically synthesized adducts that closely resemble the proteolyzed Schiff base 3'-histone-DPCs. Here, we report another two human enzymes, APE2 and TREX2, that have a similar function.