2izo | pdb_00002izo
Structure of an Archaeal PCNA1-PCNA2-FEN1 Complex
Structural highlights
FunctionFEN_SACS2 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). DNA polymerase I, DNA ligase and the flap endonuclease may be constitutively associated with the PCNA heterotrimer forming a scanning complex able to couple DNA synthesis and Okazaki fragment maturation.[1] 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 PubMedThe archaeal/eukaryotic proliferating cell nuclear antigen (PCNA) toroidal clamp interacts with a host of DNA modifying enzymes, providing a stable anchorage and enhancing their respective processivities. Given the broad range of enzymes with which PCNA has been shown to interact, relatively little is known about the mode of assembly of functionally meaningful combinations of enzymes on the PCNA clamp. We have determined the X-ray crystal structure of the Sulfolobus solfataricus PCNA1-PCNA2 heterodimer, bound to a single copy of the flap endonuclease FEN1 at 2.9 A resolution. We demonstrate the specificity of interaction of the PCNA subunits to form the PCNA1-PCNA2-PCNA3 heterotrimer, as well as providing a rationale for the specific interaction of the C-terminal PIP-box motif of FEN1 for the PCNA1 subunit. The structure explains the specificity of the individual archaeal PCNA subunits for selected repair enzyme 'clients', and provides insights into the co-ordinated assembly of sequential enzymatic steps in PCNA-scaffolded DNA repair cascades. Structure of an archaeal PCNA1-PCNA2-FEN1 complex: elucidating PCNA subunit and client enzyme specificity.,Dore AS, Kilkenny ML, Jones SA, Oliver AW, Roe SM, Bell SD, Pearl LH Nucleic Acids Res. 2006;34(16):4515-26. Epub 2006 Aug 31. PMID:16945955[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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