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RAD51 assembly on single-stranded (ss)DNAs is a crucial step in the homology-dependent repair of DNA damage for genomic stability. The formation of the RAD51 filament is promoted by various RAD51-interacting proteins including RAD51 paralogues. However, the mechanisms underlying the differential control of RAD51-filament dynamics by these factors remain largely unknown. Here, we report a role for the human RAD51 paralogue, SWSAP1, as a novel regulator of RAD51 assembly. Swsap1-deficient cells show defects in DNA damage-induced RAD51 assembly during both mitosis and meiosis. Defective RAD51 assembly in SWSAP1-depleted cells is suppressed by the depletion of FIGNL1, which binds to RAD51 as well as SWSAP1. Purified FIGNL1 promotes the dissociation of RAD51 from ssDNAs. The dismantling activity of FIGNL1 does not require its ATPase but depends on RAD51-binding. Purified SWSAP1 inhibits the RAD51-dismantling activity of FIGNL1. Taken together, our data suggest that SWSAP1 protects RAD51 filaments by antagonizing the anti-recombinase, FIGNL1.
This article was published in the following journal.
Name: Nature communications
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A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.
A Fanconi anemia complementation group protein that contains an N-terminal DNA-binding region and seven, C-terminal, WD REPEATS. It is an essential factor in HOMOLOGOUS RECOMBINATION DNA REPAIR through its interactions with BRCA2 PROTEIN; RAD51 RECOMBINASE; and BRCA1 PROTEIN. It functions as a molecular scaffold to localize and stabilize these proteins at homologous recombination sites. Mutations in the PALB2 gene are associated with FANCONI ANEMIA complementation group N; type 3 PANCREATIC NEOPLASMS; and susceptibility to BREAST CANCER.
Type III intermediate filament proteins that assemble into neurofilaments, the major cytoskeletal element in nerve axons and dendrites. They consist of three distinct polypeptides, the neurofilament triplet. Types I, II, and IV intermediate filament proteins form other cytoskeletal elements such as keratins and lamins. It appears that the metabolism of neurofilaments is disturbed in Alzheimer's disease, as indicated by the presence of neurofilament epitopes in the neurofibrillary tangles, as well as by the severe reduction of the expression of the gene for the light neurofilament subunit of the neurofilament triplet in brains of Alzheimer's patients. (Can J Neurol Sci 1990 Aug;17(3):302)
An APOPTOSIS-regulating protein that is structurally related to CASPASE 8 and competes with CASPASE 8 for binding to FAS ASSOCIATED DEATH DOMAIN PROTEIN. Two forms of CASP8 and FADD-like apoptosis regulating protein exist, a long form containing a caspase-like enzymatically inactive domain and a short form which lacks the caspase-like domain.
A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...