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Structural basis for recruitment of human flap endonuclease 1 to PCNA.


ABSTRACT: 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 beta-strands connected by a short helix, the betaA-alphaA-betaB motif, participating in beta-beta 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.

SUBMITTER: Sakurai S 

PROVIDER: S-EPMC549611 | biostudies-literature | 2005 Feb

REPOSITORIES: biostudies-literature

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Structural basis for recruitment of human flap endonuclease 1 to PCNA.

Sakurai Shigeru S   Kitano Ken K   Yamaguchi Hiroto H   Hamada Keisuke K   Okada Kengo K   Fukuda Kotaro K   Uchida Makiyo M   Ohtsuka Eiko E   Morioka Hiroshi H   Hakoshima Toshio T  

The EMBO journal 20041216 4


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 beta-strands connected by a short helix, the betaA-alphaA-betaB motif, participating in beta-beta and hydr  ...[more]

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