Nucleic Acids Research Advance Access originally published online on August 31, 2006
Nucleic Acids Research 2006 34(16):4515-4526; doi:10.1093/nar/gkl623
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Nucleic Acids Research, 2006, Vol. 34, No. 16 4515-4526
© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Structural Biology |
Structure of an archaeal PCNA1–PCNA2–FEN1 complex: elucidating PCNA subunit and client enzyme specificity
CR-UK DNA Repair Enzymes Group, Section of Structural Biology, The Institute of Cancer Research 237 Fulham Road, Chelsea, London, SW3 6JB, UK 1 MRC Cancer Cell Unit, Hutchison MRC Research Centre Hills Road, Cambridge, CB2 2XZ, UK
*To whom correspondence should be addressed. Tel: +44 207 153 5453; Fax: +44 207 153 5457; Email: Andrew.Dore{at}icr.ac.uk
Received May 2, 2006. Revised August 8, 2006. Accepted August 8, 2006.
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 Å 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.
Correspondence may also be addressed to Laurence H. Pearl. Tel: +44 207 153 5443; Fax: +44 207 153 5457; Email: Laurence.Pearl{at}icr.ac.uk
Present address: Sarah A. Jones, Cancer Research UK, Genome Stability Laboratory, Clare Hall Laboratories, Blanche Lane, South Mimms, Herts, EN6 3LD, UK
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