title: Promotion of homologous recombination and genomic stability by RAD51AP1 via RAD51 recombinase enhancement.
abstract: Homologous recombination (HR) repairs chromosome damage and is indispensable for tumor suppression in humans. RAD51 mediates the DNA strand-pairing step in HR. RAD51 associated protein 1 (RAD51AP1) is a RAD51-interacting protein whose function has remained elusive. Knockdown of RAD51AP1 in human cells by RNA interference engenders sensitivity to different types of genotoxic stress, and RAD51AP1 is epistatic to the HR protein XRCC3. Moreover, RAD51AP1-depleted cells are impaired for the recombinational repair of a DNA double-strand break and exhibit chromatid breaks both spontaneously and upon DNA-damaging treatment. Purified RAD51AP1 binds both dsDNA and a D loop structure and, only when able to interact with RAD51, greatly stimulates the RAD51-mediated D loop reaction. Biochemical and cytological results show that RAD51AP1 functions at a step subsequent to the assembly of the RAD51-ssDNA nucleoprotein filament. Our findings provide evidence that RAD51AP1 helps maintain genomic integrity via RAD51 recombinase enhancement.
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Wiese
authors.forename: Eloïse
authors.initials: E
authors.lastname: Dray
authors.forename: Torsten
authors.initials: T
authors.lastname: Groesser
authors.forename: Joseph
authors.initials: J
authors.lastname: San Filippo
authors.forename: Idina
authors.initials: I
authors.lastname: Shi
authors.forename: David W
authors.initials: DW
authors.lastname: Collins
authors.forename: Miaw-Sheue
authors.initials: MS
authors.lastname: Tsai
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Williams
authors.forename: Bjorn
authors.initials: B
authors.lastname: Rydberg
authors.forename: Patrick
authors.initials: P
authors.lastname: Sung
authors.forename: David
authors.initials: D
authors.lastname: Schild
mesh_terms: D002842:Chromatids / Q000378:metabolism; D053960:DNA Breaks; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D042822:Genomic Instability; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D009690:Nucleic Acid Conformation; D016601:RNA-Binding Proteins; D051135:Rad51 Recombinase / Q000378:metabolism*; D011995:Recombination, Genetic
chemical_list: D004268:DNA-Binding Proteins; C110410:RAD51AP1 protein, human; D016601:RNA-Binding Proteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase