Title: A role for the base excision repair enzyme NEIL3 in replication-dependent repair of interstrand DNA cross-links derived from psoralen and abasic sites.

Authors: Yang, Zhiyu; Nejad, Maryam Imani; Varela, Jacqueline Gamboa; Price, Nathan E; Wang, Yinsheng; Gates, Kent S

Published In DNA Repair (Amst), (2017 04)

Abstract: Interstrand DNA-DNA cross-links are highly toxic lesions that are important in medicinal chemistry, toxicology, and endogenous biology. In current models of replication-dependent repair, stalling of a replication fork activates the Fanconi anemia pathway and cross-links are "unhooked" by the action of structure-specific endonucleases such as XPF-ERCC1 that make incisions flanking the cross-link. This process generates a double-strand break, which must be subsequently repaired by homologous recombination. Recent work provided evidence for a new, incision-independent unhooking mechanism involving intrusion of a base excision repair (BER) enzyme, NEIL3, into the world of cross-link repair. The evidence suggests that the glycosylase action of NEIL3 unhooks interstrand cross-links derived from an abasic site or the psoralen derivative trioxsalen. If the incision-independent NEIL3 pathway is blocked, repair reverts to the incision-dependent route. In light of the new model invoking participation of NEIL3 in cross-link repair, we consider the possibility that various BER glycosylases or other DNA-processing enzymes might participate in the unhooking of chemically diverse interstrand DNA cross-links.

PubMed ID: 28262582

MeSH Terms: Animals; Cross-Linking Reagents/toxicity; DNA Adducts/metabolism*; DNA Damage*; DNA Repair*; Furocoumarins/metabolism*; Humans; N-Glycosyl Hydrolases/metabolism*