title: Human DNA helicase B functions in cellular homologous recombination and stimulates Rad51-mediated 5'-3' heteroduplex extension in vitro.
abstract: Homologous recombination is involved in the repair of DNA damage and collapsed replication fork, and is critical for the maintenance of genomic stability. Its process involves a network of proteins with different enzymatic activities. Human DNA helicase B (HDHB) is a robust 5'-3' DNA helicase which accumulates on chromatin in cells exposed to DNA damage. HDHB facilitates cellular recovery from replication stress, but its role in DNA damage response remains unclear. Here we report that HDHB silencing results in reduced sister chromatid exchange, impaired homologous recombination repair, and delayed RPA late-stage foci formation induced by ionizing radiation. Ectopically expressed HDHB colocalizes with Rad51, Rad52, RPA, and ssDNA. In vitro, HDHB stimulates Rad51-mediated heteroduplex extension in 5'-3' direction. A helicase-defective mutant HDHB failed to promote this reaction. Our studies implicate HDHB promotes homologous recombination in vivo and stimulates 5'-3' heteroduplex extension during Rad51-mediated strand exchange in vitro.
authors.affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Hanjian
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Peijun
authors.initials: P
authors.lastname: Yan
authors.affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Ellen
authors.initials: E
authors.lastname: Fanning
mesh_terms: D045744:Cell Line, Tumor; D002842:Chromatids / Q000235:genetics / Q000528:radiation effects; D004247:DNA / Q000235:genetics*; D004249:DNA Damage; D004265:DNA Helicases / Q000378:metabolism*; D004260:DNA Repair / Q000528:radiation effects; D004277:DNA, Single-Stranded / Q000235:genetics; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D059765:Homologous Recombination / Q000528:radiation effects; D006801:Humans; D009692:Nucleic Acid Heteroduplexes / Q000235:genetics*; D021381:Protein Transport / Q000528:radiation effects; D051135:Rad51 Recombinase / Q000378:metabolism*; D051721:Rad52 DNA Repair and Recombination Protein / Q000378:metabolism; D051716:Replication Protein A / Q000378:metabolism
chemical_list: D004277:DNA, Single-Stranded; D009692:Nucleic Acid Heteroduplexes; D051721:Rad52 DNA Repair and Recombination Protein; D051716:Replication Protein A; D004247:DNA; D051135:Rad51 Recombinase; D015252:Deoxyribonucleases, Type II Site-Specific; C484263:HELB protein, human; D004265:DNA Helicases