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- W1994561103 abstract "Flap EndoNuclease-1 (FEN-1) and the processivity factor proliferating cell nuclear antigen (PCNA) are central to DNA replication and repair. To clarify the molecular basis of FEN-1 specificity and PCNA activation, we report here structures of FEN-1:DNA and PCNA:FEN-1-peptide complexes, along with fluorescence resonance energy transfer (FRET) and mutational results. FEN-1 binds the unpaired 3′ DNA end (3′ flap), opens and kinks the DNA, and promotes conformational closing of a flexible helical clamp to facilitate 5′ cleavage specificity. Ordering of unstructured C-terminal regions in FEN-1 and PCNA creates an intermolecular β sheet interface that directly links adjacent PCNA and DNA binding regions of FEN-1 and suggests how PCNA stimulates FEN-1 activity. The DNA and protein conformational changes, composite complex structures, FRET, and mutational results support enzyme-PCNA alignments and a kinked DNA pivot point that appear suitable to coordinate rotary handoffs of kinked DNA intermediates among enzymes localized by the three PCNA binding sites." @default.
- W1994561103 created "2016-06-24" @default.
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- W1994561103 date "2004-01-01" @default.
- W1994561103 modified "2023-10-15" @default.
- W1994561103 title "Structural Basis for FEN-1 Substrate Specificity and PCNA-Mediated Activation in DNA Replication and Repair" @default.
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- W1994561103 doi "https://doi.org/10.1016/s0092-8674(03)01036-5" @default.
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