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. 2009 Oct 9;106(43):18201–18206. doi: 10.1073/pnas.0907280106

Fig. 4.

Fig. 4.

Model for the MUTYH initiated long patch BER of 8-oxo-G, after misincorporation by the replication machinery. 1) DNA replication over an 8-oxo-G by DNA pol δ. 2) recognition of an A:8-oxo-G mispair by MUTYH, removal of the A and formation of an AP site (designated as B). 3) recruitment of APE1 mediated by MUTYH/PCNA and generation of 5′-P, 3′-OH gapped intermediate. 4) protection of the 1-nt gap by RP-A and PCNA mediated recruitment of DNA pol λ, with accurate gap filling (dCTP incorporation). 5) PCNA mediated recruitment of FEN1 and removal of 1-nt flap. 6) ligation of the nick by recruited DNA ligase I and further faithful OGG1 initiated DNA pol β mediated SP-BER of C:8-oxo-G product. Alternatively an inaccurate loop is initiated: (A) DNA pol λ catalyzes inaccurate gap filling; (B) recruitment of DNA ligase III/XRCC1-mediated by PCNA and ligation of the nick; (C) recognition of A:8-oxo-G mispair by MUTYH, removal of A and generation of AP site (designated as B); and (D) recruitment of APE1 mediated by MUTYH/PCNA, generation of 5′-P, 3′-OH gapped intermediate. This creates an opportunity for DNA pol λ to catalyze accurate LP-BER. For further details, see text.