title: Mechanistic insights into RAD51-associated protein 1 (RAD51AP1) action in homologous DNA repair.
abstract: Homologous recombination catalyzed by the RAD51 recombinase is essential for maintaining genome integrity upon the induction of DNA double strand breaks and other DNA lesions. By enhancing the recombinase activity of RAD51, RAD51AP1 (RAD51-associated protein 1) serves a key role in homologous recombination-mediated chromosome damage repair. We show here that RAD51AP1 harbors two distinct DNA binding domains that are both needed for maximal protein activity under physiological conditions. We have finely mapped the two DNA binding domains in RAD51AP1 and generated mutant variants that are impaired in either or both of the DNA binding domains. Examination of these mutants reveals that both domains are indispensable for RAD51AP1 function in cells. These and other results illuminate the mechanistic basis of RAD51AP1 action in homologous DNA repair.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Myun Hwa
authors.initials: MH
authors.lastname: Dunlop
authors.forename: Eloïse
authors.initials: E
authors.lastname: Dray
authors.forename: Weixing
authors.initials: W
authors.lastname: Zhao
authors.forename: Joseph
authors.initials: J
authors.lastname: San Filippo
authors.forename: Miaw-Sheue
authors.initials: MS
authors.lastname: Tsai
authors.forename: Stanley G
authors.initials: SG
authors.lastname: Leung
authors.forename: David
authors.initials: D
authors.lastname: Schild
authors.forename: Claudia
authors.initials: C
authors.lastname: Wiese
authors.forename: Patrick
authors.initials: P
authors.lastname: Sung
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D017124:Conserved Sequence; D004247:DNA / Q000737:chemistry; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D010449:Peptide Mapping; D010641:Phenotype; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D017384:Sequence Deletion
chemical_list: D004268:DNA-Binding Proteins; D010446:Peptide Fragments; C110410:RAD51AP1 protein, human; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D004247:DNA