| Structural highlights
Disease
FBH1_HUMAN Defects in FBH1 are frequently observed in melanomas, resulting in increased survival in response to replicative stress. Its inactivation may play a role in oncogenic transformation.[1]
Function
FBH1_HUMAN 3'-5' DNA helicase and substrate-recognition component of the SCF(FBH1) E3 ubiquitin ligase complex that plays a key role in response to stalled/damaged replication forks (PubMed:11956208, PubMed:23393192). Involved in genome maintenance by acting as an anti-recombinogenic helicase and preventing extensive strand exchange during homologous recombination: promotes RAD51 filament dissolution from stalled forks, thereby inhibiting homologous recombination and preventing excessive recombination (PubMed:17724085, PubMed:19736316). Also promotes cell death and DNA double-strand breakage in response to replication stress: together with MUS81, promotes the endonucleolytic DNA cleavage following prolonged replication stress via its helicase activity, possibly to eliminate cells with excessive replication stress (PubMed:23319600, PubMed:23361013). Plays a major role in remodeling of stalled DNA forks by catalyzing fork regression, in which the fork reverses and the two nascent DNA strands anneal (PubMed:25772361). In addition to the helicase activity, also acts as the substrate-recognition component of the SCF(FBH1) E3 ubiquitin ligase complex, a complex that mediates ubiquitination of RAD51, leading to regulate RAD51 subcellular location (PubMed:25585578).[2] [3] [4] [5] [6] [7] [8]
References
- ↑ Jeong YT, Cermak L, Guijarro MV, Hernando E, Pagano M. FBH1 protects melanocytes from transformation and is deregulated in melanomas. Cell Cycle. 2013 Apr 1;12(7):1128-32. PMID:23466708 doi:10.4161/cc.24165
- ↑ Kim J, Kim JH, Lee SH, Kim DH, Kang HY, Bae SH, Pan ZQ, Seo YS. The novel human DNA helicase hFBH1 is an F-box protein. J Biol Chem. 2002 Jul 5;277(27):24530-7. PMID:11956208 doi:10.1074/jbc.M201612200
- ↑ Chiolo I, Saponaro M, Baryshnikova A, Kim JH, Seo YS, Liberi G. The human F-Box DNA helicase FBH1 faces Saccharomyces cerevisiae Srs2 and postreplication repair pathway roles. Mol Cell Biol. 2007 Nov;27(21):7439-50. PMID:17724085 doi:10.1128/MCB.00963-07
- ↑ Fugger K, Mistrik M, Danielsen JR, Dinant C, Falck J, Bartek J, Lukas J, Mailand N. Human Fbh1 helicase contributes to genome maintenance via pro anti-recombinase activities. J Cell Biol. 2009 Sep 7;186(5):655-63. PMID:19736316 doi:10.1083/jcb.200812138
- ↑ Jeong YT, Rossi M, Cermak L, Saraf A, Florens L, Washburn MP, Sung P, Schildkraut CL, Pagano M. FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA replication stress. J Cell Biol. 2013 Jan 21;200(2):141-9. PMID:23319600 doi:10.1083/jcb.201209002
- ↑ Fugger K, Chu WK, Haahr P, Kousholt AN, Beck H, Payne MJ, Hanada K, Hickson ID, Sørensen CS. FBH1 co-operates with MUS81 in inducing DNA double-strand breaks and cell death following replication stress. Nat Commun. 2013;4:1423. PMID:23361013 doi:10.1038/ncomms2395
- ↑ Chu WK, Payne MJ, Beli P, Hanada K, Choudhary C, Hickson ID. FBH1 influences DNA replication fork stability and homologous recombination through ubiquitylation of RAD51. Nat Commun. 2015 Jan 14;6:5931. PMID:25585578 doi:10.1038/ncomms6931
- ↑ Fugger K, Mistrik M, Neelsen KJ, Yao Q, Zellweger R, Kousholt AN, Haahr P, Chu WK, Bartek J, Lopes M, Hickson ID, Sørensen CS. FBH1 Catalyzes Regression of Stalled Replication Forks. Cell Rep. 2015 Mar 17;10(10):1749-1757. PMID:25772361 doi:10.1016/j.celrep.2015.02.028
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