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Bacteria-to-Human Protein Networks Reveal Origins of Endogenous DNA Damage.
Xia, Jun; Chiu, Li-Ya; Nehring, Ralf B; Bravo Núñez, María Angélica; Mei, Qian; Perez, Mercedes; Zhai, Yin; Fitzgerald, Devon M; Pribis, John P; Wang, Yumeng; Hu, Chenyue W; Powell, Reid T; LaBonte, Sandra A; Jalali, Ali; Matadamas Guzmán, Meztli L; Lentzsch, Alfred M; Szafran, Adam T; Joshi, Mohan C; Richters, Megan; Gibson, Janet L; Frisch, Ryan L; Hastings, P J; Bates, David; Queitsch, Christine; Hilsenbeck, Susan G; Coarfa, Cristian; Hu, James C; Siegele, Deborah A; Scott, Kenneth L; Liang, Han; Mancini, Michael A; Herman, Christophe; Miller, Kyle M; Rosenberg, Susan M.
Affiliation
  • Xia J; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA;
  • Chiu LY; Department of Molecular Biosciences, LIVESTRONG Cancer Institute of the Dell Medical School, University of Texas at Austin, Austin, TX 78712, USA.
  • Nehring RB; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA;
  • Bravo Núñez MA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biochemistry and 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 and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA;
  • Perez M; Department of Molecular Biosciences, LIVESTRONG Cancer Institute of the Dell Medical School, University of Texas at Austin, Austin, TX 78712, USA.
  • Zhai Y; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, 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 and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA;
  • Pribis JP; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA;
  • Wang Y; Graduate Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, TX 77030, USA; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Hu CW; Department of Bioengineering, Rice University, Houston, TX 77030, USA.
  • Powell RT; Institute of Biosciences and Technology, Texas A&M University, Houston, TX 77030, USA.
  • LaBonte SA; Department of Biochemistry and Biophysics, Texas A&M University and Texas AgriLife Research, College Station, TX 77843, USA.
  • Jalali A; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA.
  • Matadamas Guzmán ML; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA;
  • Lentzsch AM; Department of Molecular Biosciences, LIVESTRONG Cancer Institute of the Dell Medical School, University of Texas at Austin, Austin, TX 78712, USA.
  • Szafran AT; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
  • Joshi MC; 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.
  • Richters M; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA;
  • Gibson JL; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA;
  • Frisch RL; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA;
  • 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.
  • 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.
  • Queitsch C; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
  • Hilsenbeck SG; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Coarfa C; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
  • Hu JC; Department of Biochemistry and Biophysics, Texas A&M University and Texas AgriLife Research, College Station, TX 77843, USA.
  • Siegele DA; Department of Biology, Texas A&M University, College Station, TX 77843, USA.
  • Scott KL; 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; Graduate Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, TX 77
  • Liang H; Graduate Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, TX 77030, USA; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Systems Biology, The University of Texa
  • Mancini MA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, 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; Graduate Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Housto
  • Miller KM; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Biosciences, LIVESTRONG Cancer Institute of the Dell Medical School, University of Texas at Austin, Austin, TX 78712, USA. Electronic address: kyle.miller@austin.utexas.edu.
  • Rosenberg SM; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA;
Cell ; 176(1-2): 127-143.e24, 2019 01 10.
Article in En | MEDLINE | ID: mdl-30633903
ABSTRACT
DNA damage provokes mutations and cancer and results from external carcinogens or endogenous cellular processes. However, the intrinsic instigators of endogenous DNA damage are poorly understood. Here, we identify proteins that promote endogenous DNA damage when overproduced the DNA "damage-up" proteins (DDPs). We discover a large network of DDPs in Escherichia coli and deconvolute them into six function clusters, demonstrating DDP mechanisms in three reactive oxygen increase by transmembrane transporters, chromosome loss by replisome binding, and replication stalling by transcription factors. Their 284 human homologs are over-represented among known cancer drivers, and their RNAs in tumors predict heavy mutagenesis and a poor prognosis. Half of the tested human homologs promote DNA damage and mutation when overproduced in human cells, with DNA damage-elevating mechanisms like those in E. coli. Our work identifies networks of DDPs that provoke endogenous DNA damage and may reveal DNA damage-associated functions of many human known and newly implicated cancer-promoting proteins.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: DNA Damage / DNA Repair Type of study: Prognostic_studies Limits: Humans Language: En Journal: Cell Year: 2019 Type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: DNA Damage / DNA Repair Type of study: Prognostic_studies Limits: Humans Language: En Journal: Cell Year: 2019 Type: Article