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Holliday junction trap shows how cells use recombination and a junction-guardian role of RecQ helicase.
Xia, Jun; Chen, Li-Tzu; Mei, Qian; Ma, Chien-Hui; Halliday, Jennifer A; Lin, Hsin-Yu; Magnan, David; Pribis, John P; Fitzgerald, Devon M; Hamilton, Holly M; Richters, Megan; Nehring, Ralf B; Shen, Xi; Li, Lei; Bates, David; Hastings, P J; Herman, Christophe; Jayaram, Makkuni; Rosenberg, Susan M.
Afiliación
  • Xia J; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Biochemistry, Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.;
  • Chen LT; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Biochemistry, Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.;
  • Mei Q; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Biochemistry, Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.;
  • Ma CH; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.; Institute of Cell and Molecular Biology, University of Texas, Austin, TX 78712, USA.
  • Halliday JA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Lin HY; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Biochemistry, Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.;
  • Magnan D; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.; Grad
  • Pribis JP; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Biochemistry, Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.;
  • Fitzgerald DM; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Biochemistry, Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.;
  • Hamilton HM; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Biochemistry, Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.;
  • Richters M; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Biochemistry, Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.;
  • Nehring RB; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Biochemistry, Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.;
  • Shen X; Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Li L; Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Bates D; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.; Grad
  • Hastings PJ; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Herman C; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.; Grad
  • Jayaram M; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.; Institute of Cell and Molecular Biology, University of Texas, Austin, TX 78712, USA.
  • Rosenberg SM; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Biochemistry, Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.;
Sci Adv ; 2(11): e1601605, 2016 Nov.
Article en En | MEDLINE | ID: mdl-28090586
DNA repair by homologous recombination (HR) underpins cell survival and fuels genome instability, cancer, and evolution. However, the main kinds and sources of DNA damage repaired by HR in somatic cells and the roles of important HR proteins remain elusive. We present engineered proteins that trap, map, and quantify Holliday junctions (HJs), a central DNA intermediate in HR, based on catalytically deficient mutant RuvC protein of Escherichia coli. We use RuvCDefGFP (RDG) to map genomic footprints of HR at defined DNA breaks in E. coli and demonstrate genome-scale directionality of double-strand break (DSB) repair along the chromosome. Unexpectedly, most spontaneous HR-HJ foci are instigated, not by DSBs, but rather by single-stranded DNA damage generated by replication. We show that RecQ, the E. coli ortholog of five human cancer proteins, nonredundantly promotes HR-HJ formation in single cells and, in a novel junction-guardian role, also prevents apparent non-HR-HJs promoted by RecA overproduction. We propose that one or more human RecQ orthologs may act similarly in human cancers overexpressing the RecA ortholog RAD51 and find that cancer genome expression data implicate the orthologs BLM and RECQL4 in conjunction with EME1 and GEN1 as probable HJ reducers in such cancers. Our results support RecA-overproducing E. coli as a model of the many human tumors with up-regulated RAD51 and provide the first glimpses of important, previously elusive reaction intermediates in DNA replication and repair in single living cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Recombinación Genética / ADN Bacteriano / ADN Cruciforme / Escherichia coli / RecQ Helicasas / Roturas del ADN de Cadena Simple Límite: Humans Idioma: En Revista: Sci Adv Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Recombinación Genética / ADN Bacteriano / ADN Cruciforme / Escherichia coli / RecQ Helicasas / Roturas del ADN de Cadena Simple Límite: Humans Idioma: En Revista: Sci Adv Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos