A gene involved in control of human cellular senescence on human chromosome 1q

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Published in:	Molecular and Cellular Biology Vol. 14; no. 4; pp. 2291 - 2297
Main Authors:	Hensler, P J, Annab, L A, Barrett, J C, Pereira-Smith, O M
Format:	Journal Article
Language:	English
Published:	Washington, DC American Society for Microbiology 01-04-1994
Subjects:	550400 - Genetics 550900 - Pathology AGING ANIMAL CELLS BASIC BIOLOGICAL SCIENCES Biological and medical sciences Bone Neoplasms Cell Division - genetics Cell Line Cell Line, Transformed cell lines cell proliferation Cellular Senescence - genetics chromosome 1 Chromosome Mapping CHROMOSOMES Chromosomes, Human, Pair 1 Classical genetics, quantitative genetics, hybrids Clone Cells complementation Cytomegalovirus - genetics Fundamental and applied biological sciences. Psychology GENE REGULATION genes Genes, ras Genetic Complementation Test GENETIC MAPPING Genetics of eukaryotes. Biological and molecular evolution Human HUMAN CHROMOSOME 1 HUMAN CHROMOSOMES Humans man MAPPING Molecular Sequence Data Osteosarcoma senescence Tumor Cells, Cultured Human Senescence Genetic inheritance Cell line Ageing Cytogenetics Locus Chromosome G banding A1-Chromosome
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Abstract	Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue MCB About MCB Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy MCB RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0270-7306 Online ISSN: 1098-5549 Copyright © 2014 by the American Society for Microbiology. For an alternate route to MCB .asm.org, visit: MCB
AbstractList	Normal cells in culture exhibit limited division potential and have been used as a model for cellular senescence. In contrast, tumor-derived or carcinogen- or virus-transformed cells are capable of indefinite division. Fusion of normal human diploid fibroblasts with immortal human cells yielded hybrids having limited life spans, indicating that cellular senescence was dominant. Fusions of various immortal human cell lines with each other led to the identification of four complementation groups for indefinite division. The purpose of this study was to determine whether human chromosome 1 could complement the recessive immortal defect of human cell lines assigned to one of the four complementation groups. Using microcell fusion, we introduced a single normal human chromosome 1 into immortal human cell lines representing the complementation groups and determined that it caused loss of proliferative potential of an osteosarcoma-derived cell line (TE85), a cytomegalovirus-transformed lung fibroblast cell line (CMV-Mj-HEL-1), and a Ki-ras(+)-transformed derivative of TE85 (143B TK-), all of which were assigned to complementation group C. This chromosome 1 caused no change in proliferative potential of cell lines representing the other complementation groups. A derivative of human chromosome 1 that had lost most of the q arm by spontaneous deletion was unable to induce senescence in any of the immortal cell lines. This finding indicates that the q arm of human chromosome 1 carries a gene or set of genes which is altered in the cell lines assigned to complementation group C and is involved in the control of cellular senescence. Normal cells in culture exhibit limited division potential and have been used as a model for cellular senescence. In contrast, tumor-derived or carcinogen- or virus-transformed cells are capable of indefinite division. Fusion of normal human diploid fibroblasts with immortal human cells yielded hybrids having limited life spans, indicating that cellular senescence was dominant. Fusions of various immortal human cell lines with each other led to the identification of four complementation groups for indefinite division. The purpose of this study was to determine whether human chromosome 1 could complement the recessive immortal defect of human cell lines assigned to one of the four complementation groups. Using microcell fusion, the authors introduced a single normal human chromosome 1 into immortal human cell lines representing the complementation groups and determined that it caused loss of proliferative potential of an osteosarcoma-derived cell line (TE85), a cytomegalovirus-transformed lung fibroblast cell line (CMV-Mj-HEL-1), and a Ki-ras[sup +]-transformed derivative of TE85 (143B TK[sup [minus]]), all of which were assigned to complementation group C. This chromosome 1 caused no change in proliferative potential of cell lines representing the other complementation groups. A derivative of human chromosome 1 that had lost most of the q arm by spontaneous deletion was unable to induce senescence in any of the immortal cell lines. This finding indicates that the q arm of human chromosome 1 carries a gene or set of genes which is altered in the cell lines assigned to complementation group C and is involved in the control of cellular senescence. 33 refs., 5 figs., 3 tabs. Normal cells in culture exhibit limited division potential and have been used as a model for cellular senescence. In contrast, tumor-derived or carcinogen- or virus-transformed cells are capable of indefinite division. Fusion of normal human diploid fibroblasts with immortal human cells yielded hybrids having limited life spans, indicating that cellular senescence was dominant. Fusions of various immortal human cell lines with each other led to the identification of four complementation groups for indefinite division. The purpose of this study was to determine whether human chromosome 1 could complement the recessive immortal defect of human cell lines assigned to one of the four complementation groups. Using microcell fusion, we introduced a single normal human chromosome 1 into immortal human cell lines representing the complementation groups and determined that it caused loss of proliferative potential of an osteosarcoma-derived cell line (TE85), a cytomegalovirus-transformed lung fibroblast cell line (CMV-Mj-HEL-1), and a Ki-ras super(+)-transformed derivatives of TE85 (143B TK super(-)), all of which were assigned to complementation group C. This chromosome 1 caused no change in proliferative potential of cell lines representing the other complementation groups. A derivative of human chromosome 1 that had lost most of the q arm by spontaneous deletion was unable to induce senescence in any of the immortal cell lines. This finding indicates that the q arm of human chromosome 1 carries a gene or set of genes which is altered in the cell lines assigned to complementation group and is involved in the control of cellular senescence. Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue MCB About MCB Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy MCB RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0270-7306 Online ISSN: 1098-5549 Copyright © 2014 by the American Society for Microbiology. For an alternate route to MCB .asm.org, visit: MCB
Author	P J Hensler L A Annab O M Pereira-Smith J C Barrett
AuthorAffiliation	Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030
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SubjectTerms	550400 - Genetics 550900 - Pathology AGING ANIMAL CELLS BASIC BIOLOGICAL SCIENCES Biological and medical sciences Bone Neoplasms Cell Division - genetics Cell Line Cell Line, Transformed cell lines cell proliferation Cellular Senescence - genetics chromosome 1 Chromosome Mapping CHROMOSOMES Chromosomes, Human, Pair 1 Classical genetics, quantitative genetics, hybrids Clone Cells complementation Cytomegalovirus - genetics Fundamental and applied biological sciences. Psychology GENE REGULATION genes Genes, ras Genetic Complementation Test GENETIC MAPPING Genetics of eukaryotes. Biological and molecular evolution Human HUMAN CHROMOSOME 1 HUMAN CHROMOSOMES Humans man MAPPING Molecular Sequence Data Osteosarcoma senescence Tumor Cells, Cultured
Title	A gene involved in control of human cellular senescence on human chromosome 1q
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