1rxz | pdb_00001rxz
C-terminal region of A. fulgidus FEN-1 complexed with A. fulgidus PCNA
Structural highlights
Function[PCNA_ARCFU] Sliding clamp subunit. Responsible for tethering the catalytic subunit of DNA polymerase to DNA during high-speed replication (By similarity). [FEN_ARCFU] Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. Binds the unpaired 3'-DNA end and kinks the DNA to facilitate 5' cleavage specificity. Cleaves one nucleotide into the double-stranded DNA from the junction in flap DNA, leaving a nick for ligation. Also involved in the base excision repair (BER) pathway. Acts as a genome stabilization factor that prevents flaps from equilibrating into structures that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedFlap 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 beta 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. Structural basis for FEN-1 substrate specificity and PCNA-mediated activation in DNA replication and repair.,Chapados BR, Hosfield DJ, Han S, Qiu J, Yelent B, Shen B, Tainer JA Cell. 2004 Jan 9;116(1):39-50. PMID:14718165[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences | ||||||||||||||||||||
