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| Subject Categories: Structural Biology | Genome Stability & Dynamics |
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| The EMBO Journal
(2005) 24, 683–693, doi:10.1038/sj.emboj.7600519 Published online 16 December 2004 |
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| Structural basis for recruitment of human flap endonuclease 1 to PCNA |
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| Shigeru Sakurai1, 4, Ken Kitano1, 4, Hiroto Yamaguchi2, Keisuke Hamada1, Kengo Okada1, Kotaro Fukuda3, Makiyo Uchida3, Eiko Ohtsuka3, Hiroshi Morioka3 and Toshio Hakoshima1, 2 |
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1 Structural Biology Laboratory, Nara Institute of Science and Technology, Takayama, Ikoma, Nara, Japan 2 CREST, Japan Science and Technology Agency, Takayama, Ikoma, Nara, Japan 3 Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, Japan To whom correspondence should be addressed Toshio Hakoshima, Structural Biology Laboratory, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan. Tel.: +81 743 72 5570; Fax: +81 743 72 5579; E-mail: hakosima@bs.naist.jp Hiroshi Morioka, Graduate School of Pharmaceutical Sciences, Hokkaido University, N12, W6, Kita-ku, Sapporo 060-0812, Japan. Tel.: +81 11 706 3751; Fax: +81 11 706 4989; E-mail: morioka@pharm.hokudai.ac.jp 4 These authors contributed equally to this work Received 6 September 2004; Accepted 23 November 2004; Published online 16 December 2004. |
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| Abstract |
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Flap endonuclease-1 (FEN1) is a key enzyme for maintaining genomic stability and replication. Proliferating cell nuclear antigen (PCNA) binds FEN1 and stimulates its endonuclease activity. The structural basis of the FEN1–PCNA interaction was revealed by the crystal structure of the complex between human FEN1 and PCNA. The main interface involves the C-terminal tail of FEN1, which forms two  -strands connected by a short helix, the A– A–B motif, participating in – and hydrophobic interactions with PCNA. These interactions are similar to those previously observed for the p21CIP1/WAF1 peptide. However, this structure involving the full-length enzyme has revealed additional interfaces that are involved in the core domain. The interactions at the interfaces maintain the enzyme in an inactive 'locked-down' orientation and might be utilized in rapid DNA-tracking by preserving the central hole of PCNA for sliding along the DNA. A hinge region present between the core domain and the C-terminal tail of FEN1 would play a role in switching the FEN1 orientation from an inactive to an active orientation. |
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| Keywords: DNA clamp, flap endonuclease, repair, replication, X-ray |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWS'Screw-cap' clamp loader proteins that thread Nature Structural & Molecular Biology News and Views (01 Jul 2004) Molecular biology The loader of the rings Nature News and Views (17 Jun 2004) RESEARCHStructure of an XPF endonuclease with and without DNA suggests a model for substrate recognition The EMBO Journal Article (09 Mar 2005) The EMBO Journal Article (15 Apr 1998) |
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