Chromosomal Aberrations in PARP-/- Mice: Genome Stabilization in Immortalized Cells by Reintroduction of Poly(ADP-Ribose) Polymerase cDNA
Depletion of poly(ADP-ribose) polymerase (PARP) increases the frequency of recombination, gene amplification, sister chromatid exchanges, and micronuclei formation in cells exposed to genotoxic agents, implicating PARP in the maintenance of genomic stability. Flow cytometric analysis now has reveale...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1999-11, Vol.96 (23), p.13191-13196 |
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| creator | Simbulan-Rosenthal, Cynthia M. Haddad, Bassem R. Rosenthal, Dean S. Weaver, Zoë Coleman, Allen Luo, RuiBai Young, Hannah M. Wang, Zhao-Qi Ried, Thomas Smulson, Mark E. |
| description | Depletion of poly(ADP-ribose) polymerase (PARP) increases the frequency of recombination, gene amplification, sister chromatid exchanges, and micronuclei formation in cells exposed to genotoxic agents, implicating PARP in the maintenance of genomic stability. Flow cytometric analysis now has revealed an unstable tetraploid population in immortalized fibroblasts derived from PARP-/- mice. Comparative genomic hybridization detected partial chromosomal gains in 4C5-ter, 5F-ter, and 14A1-C1 in PARP-/-mice and immortalized PARP-/-fibroblasts. Neither the chromosomal gains nor the tetraploid population were apparent in PARP-/- cells stably transfected with PARP cDNA [PARP-/-(+PARP)], indicating negative selection of cells with these genetic aberrations after reintroduction of PARP cDNA. Although the tumor suppressor p53 was not detectable in PARP-/- cells, p53 expression was partially restored in PARP-/- (+PARP) cells. Loss of 14D3-ter that encompasses the tumor suppressor gene Rb-1 in PARP-/- mice was associated with a reduction in retinoblastoma(Rb) expression; increased expression of the oncogene Jun was correlated with a gain in 4C5-ter that harbors this oncogene. These results further implicate PARP in the maintenance of genomic stability and suggest that altered expression of p53, Rb, and Jun, as well as undoubtedly many other proteins may be a result of genomic instability associated with PARP deficiency. |
| doi_str_mv | 10.1073/pnas.96.23.13191 |
| format | Article |
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Flow cytometric analysis now has revealed an unstable tetraploid population in immortalized fibroblasts derived from PARP-/- mice. Comparative genomic hybridization detected partial chromosomal gains in 4C5-ter, 5F-ter, and 14A1-C1 in PARP-/-mice and immortalized PARP-/-fibroblasts. Neither the chromosomal gains nor the tetraploid population were apparent in PARP-/- cells stably transfected with PARP cDNA [PARP-/-(+PARP)], indicating negative selection of cells with these genetic aberrations after reintroduction of PARP cDNA. Although the tumor suppressor p53 was not detectable in PARP-/- cells, p53 expression was partially restored in PARP-/- (+PARP) cells. Loss of 14D3-ter that encompasses the tumor suppressor gene Rb-1 in PARP-/- mice was associated with a reduction in retinoblastoma(Rb) expression; increased expression of the oncogene Jun was correlated with a gain in 4C5-ter that harbors this oncogene. These results further implicate PARP in the maintenance of genomic stability and suggest that altered expression of p53, Rb, and Jun, as well as undoubtedly many other proteins may be a result of genomic instability associated with PARP deficiency.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.96.23.13191</identifier><identifier>PMID: 10557296</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Animals ; Biological Sciences ; Cell Line, Transformed ; Cell lines ; Cellular biology ; Chromosome Aberrations ; Chromosomes ; Comparative genomic hybridization ; Complementary DNA ; Deoxyribonucleic acid ; Diploidy ; DNA ; DNA, Complementary ; Female ; Fibroblasts ; Gene Expression Regulation, Enzymologic - genetics ; Genes ; Genes, jun ; Genes, p53 ; Genes, Retinoblastoma ; Genome ; Genomics ; Laboratory animals ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mutation ; Nucleic Acid Hybridization ; Poly(ADP-ribose) Polymerases - genetics ; Tetraploidy ; Transfection</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1999-11, Vol.96 (23), p.13191-13196</ispartof><rights>Copyright 1993-1999 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Nov 9, 1999</rights><rights>Copyright © 1999, The National Academy of Sciences 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-f874934b5563720e54138560a0ddc02a087f39b5252c4eb4dccfb3d85203df4c3</citedby><cites>FETCH-LOGICAL-c493t-f874934b5563720e54138560a0ddc02a087f39b5252c4eb4dccfb3d85203df4c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/96/23.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/49141$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/49141$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27923,27924,53790,53792,58016,58249</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10557296$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Simbulan-Rosenthal, Cynthia M.</creatorcontrib><creatorcontrib>Haddad, Bassem R.</creatorcontrib><creatorcontrib>Rosenthal, Dean S.</creatorcontrib><creatorcontrib>Weaver, Zoë</creatorcontrib><creatorcontrib>Coleman, Allen</creatorcontrib><creatorcontrib>Luo, RuiBai</creatorcontrib><creatorcontrib>Young, Hannah M.</creatorcontrib><creatorcontrib>Wang, Zhao-Qi</creatorcontrib><creatorcontrib>Ried, Thomas</creatorcontrib><creatorcontrib>Smulson, Mark E.</creatorcontrib><title>Chromosomal Aberrations in PARP-/- Mice: Genome Stabilization in Immortalized Cells by Reintroduction of Poly(ADP-Ribose) Polymerase cDNA</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Depletion of poly(ADP-ribose) polymerase (PARP) increases the frequency of recombination, gene amplification, sister chromatid exchanges, and micronuclei formation in cells exposed to genotoxic agents, implicating PARP in the maintenance of genomic stability. Flow cytometric analysis now has revealed an unstable tetraploid population in immortalized fibroblasts derived from PARP-/- mice. Comparative genomic hybridization detected partial chromosomal gains in 4C5-ter, 5F-ter, and 14A1-C1 in PARP-/-mice and immortalized PARP-/-fibroblasts. Neither the chromosomal gains nor the tetraploid population were apparent in PARP-/- cells stably transfected with PARP cDNA [PARP-/-(+PARP)], indicating negative selection of cells with these genetic aberrations after reintroduction of PARP cDNA. Although the tumor suppressor p53 was not detectable in PARP-/- cells, p53 expression was partially restored in PARP-/- (+PARP) cells. Loss of 14D3-ter that encompasses the tumor suppressor gene Rb-1 in PARP-/- mice was associated with a reduction in retinoblastoma(Rb) expression; increased expression of the oncogene Jun was correlated with a gain in 4C5-ter that harbors this oncogene. These results further implicate PARP in the maintenance of genomic stability and suggest that altered expression of p53, Rb, and Jun, as well as undoubtedly many other proteins may be a result of genomic instability associated with PARP deficiency.</description><subject>Animals</subject><subject>Biological Sciences</subject><subject>Cell Line, Transformed</subject><subject>Cell lines</subject><subject>Cellular biology</subject><subject>Chromosome Aberrations</subject><subject>Chromosomes</subject><subject>Comparative genomic hybridization</subject><subject>Complementary DNA</subject><subject>Deoxyribonucleic acid</subject><subject>Diploidy</subject><subject>DNA</subject><subject>DNA, Complementary</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Gene Expression Regulation, Enzymologic - genetics</subject><subject>Genes</subject><subject>Genes, jun</subject><subject>Genes, p53</subject><subject>Genes, Retinoblastoma</subject><subject>Genome</subject><subject>Genomics</subject><subject>Laboratory animals</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mutation</subject><subject>Nucleic Acid Hybridization</subject><subject>Poly(ADP-ribose) Polymerases - genetics</subject><subject>Tetraploidy</subject><subject>Transfection</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFv1DAQhS0EokvhjjiAxQGVQ7ZjO05ixCXaQqlUYLXA2XIch3qVxFs7QSz_gH-Ns7tULQdOI818b_zGD6GnBOYEcna66VWYi2xO2ZwwIsg9NCMgSJKlAu6jGQDNkyKl6RF6FMIaAAQv4CE6IsB5TkU2Q78XV951LrhOtbisjPdqsK4P2PZ4Wa6WyWmCP1pt3uBz07vO4C-Dqmxrf-2wibroOucHFVumxgvTtgFXW7wyth-8q0e941yDl67dnpRny2RlKxfM612jM14Fg_XZp_IxetCoNpgnh3qMvr1_93XxIbn8fH6xKC8TnQo2JE2Rx5pWnGcsp2B4SljBM1BQ1xqogiJvmKg45VSnpkprrZuK1QWnwOom1ewYvd3v3YxVZ2ptok_Vyo23nfJb6ZSVdye9vZLf3Q9JmaAsyl8d5N5djyYMsrNBx7NVb9wYZCZonvFiAl_-A67d6Pt4mqRAmCgInyDYQ9q7ELxpbnwQkFPEcopYiiy-LncRR8nz2_5vCfaZRuDFAZikf8d3V5z8n5DN2LaD-TlE9NkeXYfB-Rs2FST--x8BBcSF</recordid><startdate>19991109</startdate><enddate>19991109</enddate><creator>Simbulan-Rosenthal, Cynthia M.</creator><creator>Haddad, Bassem R.</creator><creator>Rosenthal, Dean S.</creator><creator>Weaver, Zoë</creator><creator>Coleman, Allen</creator><creator>Luo, RuiBai</creator><creator>Young, Hannah M.</creator><creator>Wang, Zhao-Qi</creator><creator>Ried, Thomas</creator><creator>Smulson, Mark E.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</general><general>The National Academy of Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19991109</creationdate><title>Chromosomal Aberrations in PARP-/- Mice: Genome Stabilization in Immortalized Cells by Reintroduction of Poly(ADP-Ribose) Polymerase cDNA</title><author>Simbulan-Rosenthal, Cynthia M. ; 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Flow cytometric analysis now has revealed an unstable tetraploid population in immortalized fibroblasts derived from PARP-/- mice. Comparative genomic hybridization detected partial chromosomal gains in 4C5-ter, 5F-ter, and 14A1-C1 in PARP-/-mice and immortalized PARP-/-fibroblasts. Neither the chromosomal gains nor the tetraploid population were apparent in PARP-/- cells stably transfected with PARP cDNA [PARP-/-(+PARP)], indicating negative selection of cells with these genetic aberrations after reintroduction of PARP cDNA. Although the tumor suppressor p53 was not detectable in PARP-/- cells, p53 expression was partially restored in PARP-/- (+PARP) cells. Loss of 14D3-ter that encompasses the tumor suppressor gene Rb-1 in PARP-/- mice was associated with a reduction in retinoblastoma(Rb) expression; increased expression of the oncogene Jun was correlated with a gain in 4C5-ter that harbors this oncogene. These results further implicate PARP in the maintenance of genomic stability and suggest that altered expression of p53, Rb, and Jun, as well as undoubtedly many other proteins may be a result of genomic instability associated with PARP deficiency.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>10557296</pmid><doi>10.1073/pnas.96.23.13191</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Biological Sciences Cell Line, Transformed Cell lines Cellular biology Chromosome Aberrations Chromosomes Comparative genomic hybridization Complementary DNA Deoxyribonucleic acid Diploidy DNA DNA, Complementary Female Fibroblasts Gene Expression Regulation, Enzymologic - genetics Genes Genes, jun Genes, p53 Genes, Retinoblastoma Genome Genomics Laboratory animals Mice Mice, Inbred C57BL Mice, Knockout Mutation Nucleic Acid Hybridization Poly(ADP-ribose) Polymerases - genetics Tetraploidy Transfection |
| title | Chromosomal Aberrations in PARP-/- Mice: Genome Stabilization in Immortalized Cells by Reintroduction of Poly(ADP-Ribose) Polymerase cDNA |
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