title: Novel function of the Fanconi anemia group J or RECQ1 helicase to disrupt protein-DNA complexes in a replication protein A-stimulated manner.
abstract: Understanding how cellular machinery deals with chromosomal genome complexity is an important question because protein bound to DNA may affect various cellular processes of nucleic acid metabolism. DNA helicases are at the forefront of such processes, yet there is only limited knowledge how they remodel protein-DNA complexes and how these mechanisms are regulated. We have determined that representative human RecQ and Fe-S cluster DNA helicases are potently blocked by a protein-DNA interaction. The Fanconi anemia group J (FANCJ) helicase partners with the single-stranded DNA-binding protein replication protein A (RPA) to displace BamHI-E111A bound to duplex DNA in a specific manner. Protein displacement was dependent on the ATPase-driven function of the helicase and unique properties of RPA. Further biochemical studies demonstrated that the shelterin proteins TRF1 and TRF2, which preferentially bind the telomeric repeat found at chromosome ends, effectively block FANCJ from unwinding the forked duplex telomeric substrate. RPA, but not the Escherichia coli single-stranded DNA-binding protein or shelterin factor Pot1, stimulated FANCJ ejection of TRF1 from the telomeric DNA substrate. FANCJ was also able to displace TRF2 from the telomeric substrate in an RPA-dependent manner. The stimulation of helicase-catalyzed protein displacement is also observed with the DNA helicase RECQ1, suggesting a conserved functional interaction of RPA-interacting helicases. These findings suggest that partnerships between RPA and interacting human DNA helicases may greatly enhance their ability to dislodge proteins bound to duplex DNA, an activity that is likely to be highly relevant to their biological roles in DNA metabolism.
authors.affiliation: From the Laboratory of Molecular Gerontology, Biomedical Research Center, NIA, National Institutes of Health, Baltimore, Maryland 21224.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Sommers
authors.affiliation: From the Laboratory of Molecular Gerontology, Biomedical Research Center, NIA, National Institutes of Health, Baltimore, Maryland 21224.
authors.forename: Taraswi
authors.initials: T
authors.lastname: Banerjee
authors.affiliation: From the Laboratory of Molecular Gerontology, Biomedical Research Center, NIA, National Institutes of Health, Baltimore, Maryland 21224.
authors.forename: Twila
authors.initials: T
authors.lastname: Hinds
authors.affiliation: the Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, and.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Wan
authors.affiliation: the Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Wold
authors.affiliation: the Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, and.
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
authors.affiliation: From the Laboratory of Molecular Gerontology, Biomedical Research Center, NIA, National Institutes of Health, Baltimore, Maryland 21224, broshr@mail.nih.gov.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Brosh
mesh_terms: D019943:Amino Acid Substitution; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015245:Deoxyribonuclease BamHI / Q000378:metabolism; D005090:Exodeoxyribonucleases / Q000378:metabolism; D051856:Fanconi Anemia Complementation Group Proteins / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D053484:RecQ Helicases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D051716:Replication Protein A / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism; D000071657:Werner Syndrome Helicase
chemical_list: C102108:BACH1 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D051856:Fanconi Anemia Complementation Group Proteins; D046911:Macromolecular Substances; C497167:RPA1 protein, human; D011994:Recombinant Proteins; D051716:Replication Protein A; D035321:Telomeric Repeat Binding Protein 1; D004247:DNA; D005090:Exodeoxyribonucleases; D015245:Deoxyribonuclease BamHI; C506725:RECQL protein, human; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase
keywords: DNA Helicase; DNA Repair; DNA-binding Protein; FANCJ; Fanconi Anemia; Genetic Disease; Genomic Instability; RECQ1; Replication Protein A; Telomere