Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

Essential And Distinct Roles Of The F-box And Helicase Domains Of Fbh1 In DNA Damage Repair

Chikako Sakaguchi, T. Morishita, H. Shinagawa, T. Hishida
Published 2007 · Biology, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
BackgroundDNA double-strand breaks (DSBs) are induced by exogenous insults such as ionizing radiation and chemical exposure, and they can also arise as a consequence of stalled or collapsed DNA replication forks. Failure to repair DSBs can lead to genomic instability or cell death and cancer in higher eukaryotes. The Schizosaccharomyces pombe fbh1 gene encodes an F-box DNA helicase previously described to play a role in the Rhp51 (an orthologue of S. cerevisiae RAD51)-dependent recombinational repair of DSBs. Fbh1 fused to GFP localizes to discrete nuclear foci following DNA damage.ResultsTo determine the functional roles of the highly conserved F-box and helicase domains, we have characterized fbh1 mutants carrying specific mutations in these domains. We show that the F-box mutation fbh1-fb disturbs the nuclear localization of Fbh1, conferring an fbh1 null-like phenotype. Moreover, nuclear foci do not form in fbh1-fb cells with DNA damage even if Fbh1-fb is targeted to the nucleus by fusion to a nuclear localization signal sequence. In contrast, the helicase mutation fbh1-hl causes the accumulation of Fbh1 foci irrespective of the presence of DNA damage and confers damage sensitivity greater than that conferred by the null allele. Additional mutation of the F-box alleviates the hypermorphic phenotype of the fbh1-hl mutant.ConclusionThese results suggest that the F-box and DNA helicase domains play indispensable but distinct roles in Fbh1 function. Assembly of the SCFFbh1 complex is required for both the nuclear localization and DNA damage-induced focus formation of Fbh1 and is therefore prerequisite for the Fbh1 recombination function.
This paper references
Vectors for the expression of tagged proteins in Schizosaccharomyces pombe.
R. Craven (1998)
Mitotic recombination in Saccharomyces cerevisiae
F. Prado (2002)
DNA double-strand break repair: from mechanistic understanding to cancer treatment.
T. Helleday (2007)
Role of the Schizosaccharomyces pombe F-Box DNA Helicase in Processing Recombination Intermediates
T. Morishita (2005)
SCF ubiquitin protein ligases and phosphorylation-dependent proteolysis.
A. R. Willems (1999)
DNA double-strand break repair by homologous recombination.
A. Dudas (2004)
Role of Walker Motif A of RuvB Protein in Promoting Branch Migration of Holliday Junctions
T. Hishida (1999)
Fission yeast WD-repeat protein pop1 regulates genome ploidy through ubiquitin-proteasome-mediated degradation of the CDK inhibitor Rum1 and the S-phase initiator Cdc18.
K. Kominami (1997)
A DNA Helicase from Schizosaccharomyces pombeStimulated by Single-stranded DNA-binding Protein at Low ATP Concentration*
J. Park (1997)
Arrested replication fork processing: interplay between checkpoints and recombination.
S. Lambert (2007)
Sequence requirements for nuclear location of simian virus 40 large-T antigen
D. Kalderon (1984)
Combinatorial control in ubiquitin-dependent proteolysis: don't Skp the F-box hypothesis.
E. E. Patton (1998)
Role of walker motif A of RuvB protein in promoting branch migration of holliday junctions
菱田 卓 (2000)
The human F-box DNA helicase FBH1 faces S. cerevisiae Srs2 and post-replication repair pathway roles
I Chiolo (2007)
Molecular genetic analysis of fission yeast Schizosaccharomyces pombe.
S. Moreno (1991)
Identification of a family of human F-box proteins
C. Cenciarelli (1999)
The Swi5–Sfr1 complex stimulates Rhp51/Rad51 - and Dmc1-mediated DNA strand exchange in vitro
Nami Haruta (2006)
SCFhFBH1 can act as helicase and E3 ubiquitin ligase.
J. Kim (2004)
A family of mammalian F-box proteins
J. T. Winston (1999)
The F-Box DNA Helicase Fbh1 Prevents Rhp51-Dependent Recombination without Mediator Proteins
F. Osman (2005)
A Complex of Cdc4p, Skp1p, and Cdc53p/Cullin Catalyzes Ubiquitination of the Phosphorylated CDK Inhibitor Sic1p
R.M.Renny Feldman (1997)
Two different Swi5-containing protein complexes are involved in mating-type switching and recombination repair in fission yeast
Y. Akamatsu (2003)
Double‐strand break repair and homologous recombination in Schizosaccharomyces pombe
Hayatu Raji (2006)
The Srs2 helicase prevents recombination by disrupting Rad51 nucleoprotein filaments
X. Veaute (2003)
The importance of repairing stalled replication forks
M. Cox (2000)
F-Box Proteins Are Receptors that Recruit Phosphorylated Substrates to the SCF Ubiquitin-Ligase Complex
D. Skowyra (1997)
SCF and Cullin/Ring H2-based ubiquitin ligases.
R. Deshaies (1999)
Fission yeast Swi5/Sfr1 and Rhp55/Rhp57 differentially regulate Rhp51‐dependent recombination outcomes
Y. Akamatsu (2007)
DNA helicase Srs2 disrupts the Rad51 presynaptic filament
L. Krejčí (2003)
The Human F-Box DNA Helicase FBH1 Faces Saccharomyces cerevisiae Srs2 and Postreplication Repair Pathway Roles
I. Chiolo (2007)
SKP1 Connects Cell Cycle Regulators to the Ubiquitin Proteolysis Machinery through a Novel Motif, the F-Box
C. Bai (1996)
Fus3-Regulated Tec1 Degradation through SCFCdc4 Determines MAPK Signaling Specificity during Mating in Yeast
S. Chou (2004)
The Novel Human DNA Helicase hFBH1 Is an F-box Protein*
J. Kim (2002)
The Saccharomyces repair genes at the end of the century.
J. Game (2000)

This paper is referenced by
Martijn Rep Lessons from Fungal F-Box Proteins
W. Jonkers (2009)
Coupling histone homeostasis to centromere integrity via the ubiquitin-proteasome system
Yuko Takayama (2010)
FBH1 influences DNA replication fork stability and homologous recombination through ubiquitylation of RAD51.
W. Chu (2015)
Human Fbh1 helicase contributes to genome maintenance via pro- and anti-recombinase activities
Kasper Fugger (2009)
Expression and prognostic significance of Fanconi anemia group D 2 protein and breast cancer type 1 susceptibility protein in familial and sporadic breast cancer
L. Feng (2019)
The role of the F-Box protein Frp1 in pathogenicity of fusarium oxysporum
W. Jonkers (2009)
SCF Ensures Meiotic Chromosome Segregation Through a Resolution of Meiotic Recombination Intermediates
Shinya Okamoto (2012)
A failure of meiotic chromosome segregation in a fbh1Δ mutant correlates with persistent Rad51-DNA associations
Weili Sun (2011)
Significant conservation of synthetic lethal genetic interaction networks between distantly related eukaryotes
S. Dixon (2008)
Fbh1 Limits Rad51-Dependent Recombination at Blocked Replication Forks
A. Lorenz (2009)
FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA replication stress
Yeon-Tae Jeong (2013)
FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA replication stress
Yeon-Tae Jeong (2013)
MINIREVIEWS Lessons from Fungal F-Box Proteins
Wilfried Jonkers (2009)
Multiple Regulation of Rad51-Mediated Homologous Recombination by Fission Yeast Fbh1
Y. Tsutsui (2014)
Lessons from Fungal F-Box Proteins
W. Jonkers (2009)
Stress-Induced Phosphorylation of S. pombe Atf1 Abrogates Its Interaction with F Box Protein Fbh1
C. Lawrence (2009)
Emerging roles of F-box proteins in cancer drug resistance.
Linzhi Yan (2019)
Semantic Scholar Logo Some data provided by SemanticScholar