title: RAD51AP2, a novel vertebrate- and meiotic-specific protein, shares a conserved RAD51-interacting C-terminal domain with RAD51AP1/PIR51.
abstract: Many interacting proteins regulate and/or assist the activities of RAD51, a recombinase which plays a critical role in both DNA repair and meiotic recombination. Yeast two-hybrid screening of a human testis cDNA library revealed a new protein, RAD51AP2 (RAD51 Associated Protein 2), that interacts strongly with RAD51. A full-length cDNA clone predicts a novel vertebrate-specific protein of 1159 residues, and the RAD51AP2 transcript was observed only in meiotic tissue (i.e. adult testis and fetal ovary), suggesting a meiotic-specific function for RAD51AP2. In HEK293 cells the interaction of RAD51 with an ectopically-expressed recombinant large fragment of RAD51AP2 requires the C-terminal 57 residues of RAD51AP2. This RAD51-binding region shows 81% homology to the C-terminus of RAD51AP1/PIR51, an otherwise totally unrelated RAD51-binding partner that is ubiquitously expressed. Analyses using truncations and point mutations in both RAD51AP1 and RAD51AP2 demonstrate that these proteins use the same structural motif for RAD51 binding. RAD54 shares some homology with this RAD51-binding motif, but this homologous region plays only an accessory role to the adjacent main RAD51-interacting region, which has been narrowed here to 40 amino acids. A novel protein, RAD51AP2, has been discovered that interacts with RAD51 through a C-terminal motif also present in RAD51AP1.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute Boston, MA 02115, USA.
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Kovalenko
authors.forename: Claudia
authors.initials: C
authors.lastname: Wiese
authors.forename: David
authors.initials: D
authors.lastname: Schild
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004249:DNA Damage; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008540:Meiosis; D008938:Mitosis; D008969:Molecular Sequence Data; D016601:RNA-Binding Proteins; D051135:Rad51 Recombinase / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C515554:RAD51 associated protein 2, human; C110410:RAD51AP1 protein, human; D016601:RNA-Binding Proteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase