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.
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.
authors.affiliation: University of Missouri Department of Chemistry, 125 Chemistry Building Columbia, MO 65211, United States.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Yang
authors.affiliation: University of Missouri Department of Chemistry, 125 Chemistry Building Columbia, MO 65211, United States.
authors.forename: Maryam Imani
authors.initials: MI
authors.lastname: Nejad
authors.affiliation: University of Missouri Department of Chemistry, 125 Chemistry Building Columbia, MO 65211, United States.
authors.forename: Jacqueline Gamboa
authors.initials: JG
authors.lastname: Varela
authors.affiliation: University of California-Riverside, Department of Chemistry, 501 Big Springs Road Riverside, CA 92521-0403, United States.
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Price
authors.affiliation: University of California-Riverside, Department of Chemistry, 501 Big Springs Road Riverside, CA 92521-0403, United States.
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: University of Missouri Department of Chemistry, 125 Chemistry Building Columbia, MO 65211, United States; University of Missouri Department of Biochemistry, 125 Chemistry Building Columbia, MO 65211, United States. Electronic address: gatesk@missouri.edu.
authors.forename: Kent S
authors.initials: KS
authors.lastname: Gates
mesh_terms: D000818:Animals; D003432:Cross-Linking Reagents / Q000633:toxicity; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D011564:Furocoumarins / Q000378:metabolism*; D006801:Humans; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*
chemical_list: D003432:Cross-Linking Reagents; D018736:DNA Adducts; D011564:Furocoumarins; C056465:psoralen-DNA adduct; D009699:N-Glycosyl Hydrolases; C468764:NEIL3 protein, human
keywords: Abasic site; Base excision repair; Cross-link repair; DNA cross-link; Fanconi anemia; Homologous recombination; NEIL; Psoralen; XPF-ERCC1