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Storici, F; Henneke, G; Ferrari, E; Gordenin, D A; Hübscher, U; Resnick, M A (2002). The flexible loop of human FEN1 endonuclease is required for flap cleavage during DNA replication and repair. The EMBO Journal, 21(21):5930-5942.

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Abstract

The conserved, structure-specific flap endonuclease FEN1 cleaves 5' DNA flaps that arise during replication or repair. To address in vivo mechanisms of flap cleavage, we developed a screen for human FEN1 mutants that are toxic when expressed in yeast. Two targets were revealed: the flexible loop domain and the catalytic site. Toxic mutants caused G(2) arrest and cell death and were unable to repair methyl methanesulfonate lesions. All the mutant proteins retained flap binding. Unlike the catalytic site mutants, which lacked cleavage of any 5' flaps, the loop mutants exhibited partial ability to cut 5' flaps when an adjacent single nucleotide 3' flap was present. We suggest that the flexible loop is important for efficient cleavage through positioning the 5' flap and the catalytic site.

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31 citations in Web of Science®
30 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Biochemistry and Molecular Biology
DDC:570 Life sciences; biology
Language:English
Date:1 November 2002
Deposited On:11 Feb 2008 12:18
Last Modified:27 Nov 2013 18:05
Publisher:European Molecular Biology Organization ; Nature Publishing Group
ISSN:0261-4189
Publisher DOI:10.1093/emboj/cdf587
PubMed ID:12411510

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