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Model for replication-dependent interstrand cross-link repair. (a) CMG helicase collides with cross-link and dissociates. (b) Structure-specific endonucleases unhook the cross-link. (c) Homologous recombination repairs double-strand break (top duplex). Possible nuclease trimming of the oligonucleotides flanking the adduct, TLS, and extension past the adduct remnant (bottom duplex). (d) Cross-link remnant may be removed by NER.
