Article

Human Fbh1 helicase contributes to genome maintenance via pro- and anti-recombinase activities

Institute of Cancer Biology and Center for Genotoxic Stress Research, Danish Cancer Society, DK-2100 Copenhagen, Denmark.
The Journal of Cell Biology (Impact Factor: 9.83). 10/2009; 186(5):655-63. DOI: 10.1083/jcb.200812138
Source: PubMed

ABSTRACT

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.

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Available from: Jacob Falck Hansen, Apr 16, 2014
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    • "Particularly, the human Fbox DNA helicase protein 1 (FBH1) has been shown to be a key factor in fork reversal when nucleotide supply is scarce. Indeed, FBH1 accumulates at stalling forks following a short treatment of HU [112] and it is responsible for fork reversal either in vitro or in vivo [113]. Additional proteins are involved in fork reversal including SMARCAL1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein1), which appears to suppress genomic instability arising from RS. Loss of this DNAdependent ATPase leads to Schimke immunoosseous dysplasia (SIOD), a disease characterized by immunodeficiency, skeletal and kidney abnormalities [114]. "
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