期刊
JOURNAL OF CELL BIOLOGY
卷 186, 期 5, 页码 655-663出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200812138
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资金
- Danish Cancer Society
- Danish National Research Foundation
- Danish Research Council
- Czech Ministry of Education [MSMT6198959216]
- Grant Agency of the Czech Academy of Sciences [IAA501370902]
- Lundbeck Foundation [R13-A1287]
- European Commission
- John and Birthe Meyer Foundation
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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