Abstract
The RAD51 recombinase plays a central role in homologous recombination (HR), which is critical for repair of DNA double-strand breaks, maintenance of genomic stability, and prevention of developmental disorders and cancer. Here, we report the identification of an RAD51-binding protein fidgetin-like 1 (FIGNL1). FIGNL1 specifically interacts with RAD51 through its conserved RAD51 binding domain. Cells depleted of FIGNL1 show defective HR repair. Interestingly, FIGNL1 is recruited to sites of DNA damage in a manner that is independent of breast cancer 2, early onset, RAD51, and probably, RAD51 paralogs. Conversely, FIGNL1 depletion does not affect the loading of RAD51 onto ssDNA. Our additional analysis uncovered KIAA0146, also known as scaffolding protein involved in DNA repair (SPIDR), as a binding partner of FIGNL1 and established that KIAA0146/SPIDR acts with FIGNL1 in HR repair. Collectively, our study uncovers a protein complex, which consists of FIGNL1 and KIAA0146/SPIDR, in DNA repair and provides potential directions for cancer diagnosis and therapy.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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ATPases Associated with Diverse Cellular Activities
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Adenosine Triphosphatases / chemistry*
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Adenosine Triphosphatases / genetics
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Adenosine Triphosphatases / metabolism*
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Amino Acid Sequence
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Animals
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BRCA2 Protein / genetics
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BRCA2 Protein / metabolism
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Carrier Proteins / chemistry*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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DNA Damage
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DNA-Binding Proteins
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Female
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HEK293 Cells
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Histones / metabolism
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Humans
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Mice
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Microtubule-Associated Proteins
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Molecular Sequence Data
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Multiprotein Complexes / chemistry
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Multiprotein Complexes / metabolism
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Mutant Proteins / chemistry
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Mutant Proteins / genetics
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Mutant Proteins / metabolism
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Mutation
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Neoplasms / genetics
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Neoplasms / metabolism
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Nuclear Proteins / chemistry*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Protein Interaction Domains and Motifs
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Proteins / chemistry*
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Proteins / metabolism*
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Rad51 Recombinase / chemistry*
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Rad51 Recombinase / metabolism*
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Recombinational DNA Repair / genetics
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Recombinational DNA Repair / physiology*
Substances
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BRCA2 Protein
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BRCA2 protein, human
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Carrier Proteins
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DNA-Binding Proteins
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H2AX protein, human
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Histones
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Microtubule-Associated Proteins
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Multiprotein Complexes
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Mutant Proteins
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Nuclear Proteins
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Proteins
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SPIDR protein, human
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RAD51 protein, human
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Rad51 Recombinase
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Adenosine Triphosphatases
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ATPases Associated with Diverse Cellular Activities
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FIGNL1 protein, human