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

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

The Journal of cell biology (2009-09-09)
Kasper Fugger, Martin Mistrik, Jannie Rendtlew Danielsen, Christoffel Dinant, Jacob Falck, Jiri Bartek, Jiri Lukas, Niels Mailand
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.