title: Role of replication protein A in double holliday junction dissolution mediated by the BLM-Topo IIIα-RMI1-RMI2 protein complex.
abstract: The conserved BTR complex, composed of the Bloom's syndrome helicase (BLM), topoisomerase IIIα, RMI1, and RMI2, regulates homologous recombination in favor of non-crossover formation via the dissolution of the double Holliday Junction (dHJ). Here we show enhancement of the BTR-mediated dHJ dissolution reaction by the heterotrimeric single-stranded DNA binding protein replication protein A (RPA). Our results suggest that RPA acts by sequestering a single-stranded DNA intermediate during dHJ dissolution. We provide evidence that RPA physically interacts with RMI1. The RPA interaction domain in RMI1 has been mapped, and RMI1 mutants impaired for RPA interaction have been generated. Examination of these mutants ascertains the significance of the RMI1-RPA interaction in dHJ dissolution. Our results thus implicate RPA as a cofactor of the BTR complex in dHJ dissolution.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520.
authors.forename: Steven
authors.initials: S
authors.lastname: Raynard
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520.
authors.forename: Valeria
authors.initials: V
authors.lastname: Busygina
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520.
authors.forename: Akhilesh K
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520. Electronic address: patrick.sung@yale.edu.
authors.forename: Patrick
authors.initials: P
authors.lastname: Sung
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D004260:DNA Repair; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D045566:DNA, Cruciform; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D053484:RecQ Helicases / Q000378:metabolism*; D051716:Replication Protein A / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D002352:Carrier Proteins; D045566:DNA, Cruciform; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C501527:RMI1 protein, human; C533196:RMI2 protein, human; D051716:Replication Protein A; D004247:DNA; C097151:Bloom syndrome protein; D053484:RecQ Helicases; D004264:DNA Topoisomerases, Type I
keywords: Cancer Biology; DNA Binding Protein; DNA Helicase; DNA Repair; Double Holliday Junction; Homologous Recombination; Single-stranded DNA Binding Protein RPA
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