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Published online
doi:10.1083/jcb.200812138
The Journal of Cell Biology, Vol. 186, No. 5, 655-663
The Rockefeller University Press, 0021-9525 $30.00
© Fugger et al.
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Human Fbh1 helicase contributes to genome maintenance via pro- and anti-recombinase activities



Kasper Fugger1, Martin Mistrik2, Jannie Rendtlew Danielsen1, Christoffel Dinant1, Jacob Falck1, Jiri Bartek1,2, Jiri Lukas1, and Niels Mailand1

1 Institute of Cancer Biology and Center for Genotoxic Stress Research, Danish Cancer Society, DK-2100 Copenhagen, Denmark
2 Laboratory of Genomic Integrity, Palacky University, 783 71 Olomouc, Czech Republic

Correspondence to Jiri Lukas: jil{at}cancer.dk

Homologous recombination (HR) is essential for faithful repair of DNA lesions yet must be kept in check, as unrestrained HR may compromise genome integrity and lead to premature aging or cancer. To limit unscheduled HR, cells possess DNA helicases capable of preventing excessive recombination. In this study, we show that the human Fbh1 (hFbh1) helicase accumulates at sites of DNA damage or replication stress in a manner dependent fully on its helicase activity and partially on its conserved F box. hFbh1 interacted with single-stranded DNA (ssDNA), the formation of which was required for hFbh1 recruitment to DNA lesions. Conversely, depletion of endogenous Fbh1 or ectopic expression of helicase-deficient hFbh1 attenuated ssDNA production after replication block. Although elevated levels of hFbh1 impaired Rad51 recruitment to ssDNA and suppressed HR, its small interfering RNA–mediated depletion increased the levels of chromatin-associated Rad51 and caused unscheduled sister chromatid exchange. Thus, by possessing both pro- and anti-recombinogenic potential, hFbh1 may cooperate with other DNA helicases in tightly controlling cellular HR activity.

Abbreviations used in this paper: BLM, Bloom; DOX, doxycycline; DSB, double-strand break; dsDNA, double-stranded DNA; EMSA, electrophoretic mobility shift assay; hFbh1, human Fbh1; HR, homologous recombination; HU, hydroxyurea; IR, ionizing radiation; RPA, replication protein A; SCE, sister chromatid exchange; ssDNA, single-stranded DNA; WT, wild type.

© 2009 Fugger et al.
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