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PMID: 16945955 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Structure of an archaeal PCNA1-PCNA2-FEN1 complex: elucidating PCNA subunit and client enzyme specificity.

Nucleic acids research ·Vol. 34 ·No. 16 ·2006-00-00 ·Pages 4515-26

Doré AS, Kilkenny ML, Jones SA, Oliver AW, Roe SM, Bell SD, Pearl LH

Abstract

The 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.

MeSH Terms
Archaeal Proteins/chemistry,genetics Crystallography, X-Ray DNA Mutational Analysis Dimerization Flap Endonucleases/chemistry Models, Molecular Proliferating Cell Nuclear Antigen/chemistry,genetics Protein Subunits/chemistry,genetics Sulfolobus solfataricus/enzymology
Chemicals
Archaeal Proteins Proliferating Cell Nuclear Antigen Protein Subunits Flap Endonucleases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Doré Andrew S
CR-UK DNA Repair Enzymes Group, Section of Structural Biology, The Institute of Cancer Research, 237 Fulham Road, Chelsea, London, SW3 6JB, UK. Andrew.Dore@icr.ac.uk
Kilkenny Mairi L
Jones Sarah A
Oliver Antony W
Roe S Mark
Bell Stephen D
Pearl Laurence H
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkl623
Email
andrew.dore@icr.ac.uk
Published
2006-00-00
Epub
2006-00-31
Pages
4515-26
Language
English
Region
England
NLM ID
0411011
PMCID
PMC1636371
Subset
IM
Databases
PDB
2IZO
External Links
PubMed source DOI: 10.1093/nar/gkl623 PMC Full Text View journal details
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