Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract??? SMARCAL1 (also known as HARP) is a SWI/SNF family protein with an ATPase activity stimulated by DNA containing both single-stranded and double-stranded regions. Mutations in SMARCAL1 are associated with the disease Schimke immuno-osseous dysplasia, a multisystem autosomal recessive disorder characterized by T cell immunodeficiency, growth inhibition, and renal dysfunction. The cellular function of SMARCAL1, however, is unknown. Here, using Xenopus egg extracts and mass spectrometry, we identify SMARCAL1 as a protein recruited to double-stranded DNA breaks. SMARCAL1 binds to double-stranded breaks and stalled replication forks in both egg extract and human cells, specifically colocalizing with the single-stranded DNA binding factor RPA. In addition, SMARCAL1 interacts physically with RPA independently of DNA. SMARCAL1 is phosphorylated in a caffeine-sensitive manner in response to double-stranded breaks and stalled replication forks. It has been suggested that stalled forks can be stabilized by a mechanism involving caffeine-sensitive kinases, or they collapse and subsequently recruit Rad51 to promote homologous recombination repair. We show that depletion of SMARCAL1 from U2OS cells leads to increased frequency of RAD51 foci upon generation of stalled replication forks, indicating that fork breakdown is more prevalent in the absence of SMARCAL1. We propose that SMARCAL1 is a novel DNA damage-binding protein involved in replication fork stabilization.
Bachrati,
RecQ helicases: guardian angels of the DNA replication fork.
2008, Pubmed
Bachrati,
RecQ helicases: guardian angels of the DNA replication fork.
2008,
Pubmed Boerkoel,
Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.
2002,
Pubmed Boerkoel,
Manifestations and treatment of Schimke immuno-osseous dysplasia: 14 new cases and a review of the literature.
2000,
Pubmed Bohr,
Rising from the RecQ-age: the role of human RecQ helicases in genome maintenance.
2008,
Pubmed Branzei,
The checkpoint response to replication stress.
2009,
Pubmed Brosh,
Functional and physical interaction between WRN helicase and human replication protein A.
1999,
Pubmed Burgess,
Localization of recombination proteins and Srs2 reveals anti-recombinase function in vivo.
2009,
Pubmed Byun,
Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint.
2005,
Pubmed
,
Xenbase Cheok,
The Bloom's syndrome helicase promotes the annealing of complementary single-stranded DNA.
2005,
Pubmed Clewing,
Schimke immuno-osseous dysplasia: a clinicopathological correlation.
2007,
Pubmed Coleman,
Cloning and characterization of HARP/SMARCAL1: a prokaryotic HepA-related SNF2 helicase protein from human and mouse.
2000,
Pubmed Doherty,
Physical and functional mapping of the replication protein a interaction domain of the werner and bloom syndrome helicases.
2005,
Pubmed
,
Xenbase Fanning,
A dynamic model for replication protein A (RPA) function in DNA processing pathways.
2006,
Pubmed Garcia,
Human RECQ5beta, a protein with DNA helicase and strand-annealing activities in a single polypeptide.
2004,
Pubmed Golub,
Interaction of human rad51 recombination protein with single-stranded DNA binding protein, RPA.
1998,
Pubmed Hockensmith,
Purification of a calf thymus DNA-dependent adenosinetriphosphatase that prefers a primer-template junction effector.
1986,
Pubmed Hoeijmakers,
Genome maintenance mechanisms for preventing cancer.
2001,
Pubmed Jazayeri,
ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks.
2006,
Pubmed Kim,
Substrate specificities and identification of putative substrates of ATM kinase family members.
1999,
Pubmed Krejci,
DNA helicase Srs2 disrupts the Rad51 presynaptic filament.
2003,
Pubmed Leach,
Ubiquitin/SUMO modification of PCNA promotes replication fork progression in Xenopus laevis egg extracts.
2005,
Pubmed
,
Xenbase Liberi,
Rad51-dependent DNA structures accumulate at damaged replication forks in sgs1 mutants defective in the yeast ortholog of BLM RecQ helicase.
2005,
Pubmed Lisby,
Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins.
2004,
Pubmed Lopes,
The DNA replication checkpoint response stabilizes stalled replication forks.
2001,
Pubmed Machwe,
The Werner and Bloom syndrome proteins catalyze regression of a model replication fork.
2006,
Pubmed Machwe,
Replication fork regression in vitro by the Werner syndrome protein (WRN): holliday junction formation, the effect of leading arm structure and a potential role for WRN exonuclease activity.
2007,
Pubmed Matsumoto,
CIRP2, a major cytoplasmic RNA-binding protein in Xenopus oocytes.
2000,
Pubmed
,
Xenbase Matsuoka,
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.
2007,
Pubmed Meister,
Temporal separation of replication and recombination requires the intra-S checkpoint.
2005,
Pubmed Mer,
Structural basis for the recognition of DNA repair proteins UNG2, XPA, and RAD52 by replication factor RPA.
2000,
Pubmed Mimitou,
Nucleases and helicases take center stage in homologous recombination.
2009,
Pubmed Morrison,
INO80 and gamma-H2AX interaction links ATP-dependent chromatin remodeling to DNA damage repair.
2004,
Pubmed Murray,
Cell cycle extracts.
1991,
Pubmed Muthuswami,
A eukaryotic SWI2/SNF2 domain, an exquisite detector of double-stranded to single-stranded DNA transition elements.
2000,
Pubmed O'Neill,
Utilization of oriented peptide libraries to identify substrate motifs selected by ATM.
2000,
Pubmed Pacek,
A requirement for MCM7 and Cdc45 in chromosome unwinding during eukaryotic DNA replication.
2004,
Pubmed
,
Xenbase Park,
Mammalian SWI/SNF complexes facilitate DNA double-strand break repair by promoting gamma-H2AX induction.
2006,
Pubmed Paulsen,
The ATR pathway: fine-tuning the fork.
2007,
Pubmed Postow,
Ku80 removal from DNA through double strand break-induced ubiquitylation.
2008,
Pubmed
,
Xenbase Ralf,
The Bloom's syndrome helicase can promote the regression of a model replication fork.
2006,
Pubmed Rivera,
Shugoshin regulates cohesion by driving relocalization of PP2A in Xenopus extracts.
2009,
Pubmed
,
Xenbase San Filippo,
Mechanism of eukaryotic homologous recombination.
2008,
Pubmed Shaw,
Structure of RapA, a Swi2/Snf2 protein that recycles RNA polymerase during transcription.
2008,
Pubmed Shen,
The N-terminal domain of the large subunit of human replication protein A binds to Werner syndrome protein and stimulates helicase activity.
2003,
Pubmed Smith,
An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63.
2009,
Pubmed
,
Xenbase Sogo,
Fork reversal and ssDNA accumulation at stalled replication forks owing to checkpoint defects.
2002,
Pubmed Spranger,
Schimke immuno-osseous dysplasia: a newly recognized multisystem disease.
1991,
Pubmed Unsal-Kaçmaz,
The human Tim/Tipin complex coordinates an Intra-S checkpoint response to UV that slows replication fork displacement.
2007,
Pubmed Veaute,
The Srs2 helicase prevents recombination by disrupting Rad51 nucleoprotein filaments.
2003,
Pubmed Wohlschlegel,
Inhibition of eukaryotic DNA replication by geminin binding to Cdt1.
2000,
Pubmed
,
Xenbase Yusufzai,
HARP is an ATP-driven annealing helicase.
2008,
Pubmed Zou,
Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes.
2003,
Pubmed
