Regulation of nucleotide excision repair by nuclear lamin b1
The nuclear lamins play important roles in the structural organization and function of the metazoan cell nucleus. Recent studies on B-type lamins identified a requirement for lamin B1 (LB1) in the regulation of cell proliferation in normal diploid cells. In order to further investigate the function...
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description | The nuclear lamins play important roles in the structural organization and function of the metazoan cell nucleus. Recent studies on B-type lamins identified a requirement for lamin B1 (LB1) in the regulation of cell proliferation in normal diploid cells. In order to further investigate the function of LB1 in proliferation, we disrupted its normal expression in U-2 OS human osteosarcoma and other tumor cell lines. Silencing LB1 expression induced G1 cell cycle arrest without significant apoptosis. The arrested cells are unable to mount a timely and effective response to DNA damage induced by UV irradiation. Several proteins involved in the detection and repair of UV damage by the nucleotide excision repair (NER) pathway are down-regulated in LB1 silenced cells including DDB1, CSB and PCNA. We propose that LB1 regulates the DNA damage response to UV irradiation by modulating the expression of specific genes and activating persistent DNA damage signaling. Our findings are relevant to understanding the relationship between the loss of LB1 expression, DNA damage signaling, and replicative senescence. |
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Recent studies on B-type lamins identified a requirement for lamin B1 (LB1) in the regulation of cell proliferation in normal diploid cells. In order to further investigate the function of LB1 in proliferation, we disrupted its normal expression in U-2 OS human osteosarcoma and other tumor cell lines. Silencing LB1 expression induced G1 cell cycle arrest without significant apoptosis. The arrested cells are unable to mount a timely and effective response to DNA damage induced by UV irradiation. Several proteins involved in the detection and repair of UV damage by the nucleotide excision repair (NER) pathway are down-regulated in LB1 silenced cells including DDB1, CSB and PCNA. We propose that LB1 regulates the DNA damage response to UV irradiation by modulating the expression of specific genes and activating persistent DNA damage signaling. Our findings are relevant to understanding the relationship between the loss of LB1 expression, DNA damage signaling, and replicative senescence.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0069169</identifier><identifier>PMID: 23894423</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Apoptosis ; Biocompatibility ; Biology ; Biomedical materials ; Cell cycle ; Cell Cycle - genetics ; Cell Cycle - radiation effects ; Cell Cycle Checkpoints - genetics ; Cell Cycle Checkpoints - radiation effects ; Cell growth ; Cell Line, Tumor ; Cell Proliferation ; Cellular Senescence - genetics ; Cellular Senescence - radiation effects ; Damage detection ; Deoxyribonucleic acid ; DNA ; DNA damage ; DNA Damage - genetics ; DNA Damage - radiation effects ; DNA Helicases - genetics ; DNA repair ; DNA Repair - genetics ; DNA Repair - physiology ; DNA Repair Enzymes - genetics ; DNA-Binding Proteins - genetics ; Enzyme-Linked Immunosorbent Assay ; Fibroblasts ; Fluorescent Antibody Technique ; Gene expression ; Humans ; Immunoblotting ; Immunoglobulins ; Irradiation ; Kinases ; Lamin Type B - genetics ; Lamin Type B - metabolism ; Lamins ; Molecular biology ; Mutation ; Nuclei ; Nuclei (cytology) ; Nucleotide excision repair ; Osteosarcoma ; Penicillin ; Poly-ADP-Ribose Binding Proteins ; Proliferating cell nuclear antigen ; Proliferating Cell Nuclear Antigen - genetics ; Proteins ; Radiation damage ; Repair ; RNA polymerase ; Rodents ; Senescence ; Signaling ; Stem cells ; Tumor cell lines ; Ultraviolet radiation ; Ultraviolet Rays</subject><ispartof>PloS one, 2013-07, Vol.8 (7), p.e69169-e69169</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Butin-Israeli et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Butin-Israeli et al 2013 Butin-Israeli et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-569e0cdf3dc4f94c5a1383f1102fd910f045a0401fbc9078b8f734f433c743ab3</citedby><cites>FETCH-LOGICAL-c758t-569e0cdf3dc4f94c5a1383f1102fd910f045a0401fbc9078b8f734f433c743ab3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3722182/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3722182/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23894423$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Butin-Israeli, Veronika</creatorcontrib><creatorcontrib>Adam, Stephen A</creatorcontrib><creatorcontrib>Goldman, Robert D</creatorcontrib><title>Regulation of nucleotide excision repair by nuclear lamin b1</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The nuclear lamins play important roles in the structural organization and function of the metazoan cell nucleus. Recent studies on B-type lamins identified a requirement for lamin B1 (LB1) in the regulation of cell proliferation in normal diploid cells. In order to further investigate the function of LB1 in proliferation, we disrupted its normal expression in U-2 OS human osteosarcoma and other tumor cell lines. Silencing LB1 expression induced G1 cell cycle arrest without significant apoptosis. The arrested cells are unable to mount a timely and effective response to DNA damage induced by UV irradiation. Several proteins involved in the detection and repair of UV damage by the nucleotide excision repair (NER) pathway are down-regulated in LB1 silenced cells including DDB1, CSB and PCNA. We propose that LB1 regulates the DNA damage response to UV irradiation by modulating the expression of specific genes and activating persistent DNA damage signaling. Our findings are relevant to understanding the relationship between the loss of LB1 expression, DNA damage signaling, and replicative senescence.</description><subject>Analysis</subject><subject>Apoptosis</subject><subject>Biocompatibility</subject><subject>Biology</subject><subject>Biomedical materials</subject><subject>Cell cycle</subject><subject>Cell Cycle - genetics</subject><subject>Cell Cycle - radiation effects</subject><subject>Cell Cycle Checkpoints - genetics</subject><subject>Cell Cycle Checkpoints - radiation effects</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cellular Senescence - genetics</subject><subject>Cellular Senescence - radiation effects</subject><subject>Damage detection</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA damage</subject><subject>DNA Damage - genetics</subject><subject>DNA Damage - radiation effects</subject><subject>DNA Helicases - genetics</subject><subject>DNA repair</subject><subject>DNA Repair - genetics</subject><subject>DNA Repair - physiology</subject><subject>DNA Repair Enzymes - genetics</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Fibroblasts</subject><subject>Fluorescent Antibody Technique</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Immunoglobulins</subject><subject>Irradiation</subject><subject>Kinases</subject><subject>Lamin Type B - genetics</subject><subject>Lamin Type B - metabolism</subject><subject>Lamins</subject><subject>Molecular biology</subject><subject>Mutation</subject><subject>Nuclei</subject><subject>Nuclei (cytology)</subject><subject>Nucleotide excision repair</subject><subject>Osteosarcoma</subject><subject>Penicillin</subject><subject>Poly-ADP-Ribose Binding Proteins</subject><subject>Proliferating cell nuclear antigen</subject><subject>Proliferating Cell Nuclear Antigen - genetics</subject><subject>Proteins</subject><subject>Radiation damage</subject><subject>Repair</subject><subject>RNA polymerase</subject><subject>Rodents</subject><subject>Senescence</subject><subject>Signaling</subject><subject>Stem cells</subject><subject>Tumor cell lines</subject><subject>Ultraviolet radiation</subject><subject>Ultraviolet Rays</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkttq3DAQhk1paQ7tG5TWUAjtxW5HJ9uCUgihh4VAID3cClmWvFq01kayS_L2lbtOWJdcFF1IzHzzSzP6s-wVgiUiJfqw8UPopFvufKeXAAVHBX-SHSNO8KLAQJ4enI-ykxg3AIxURfE8O8Kk4pRicpx9vNbt4GRvfZd7k3eDctr3ttG5vlU2juGgd9KGvL7bZ2XIndzaLq_Ri-yZkS7ql9N-mv388vnHxbfF5dXX1cX55UKVrOoXrOAaVGNIo6jhVDGJSEUMQoBNwxEYoEwCBWRqxaGs6sqUhBpKiCopkTU5zd7sdXfORzE1HgWiuCQlZaxIxGpPNF5uxC7YrQx3wksr_gZ8aIUMvU3PFwgrUHUSN9BQMFwaVlRQ1JpQzBqMk9an6bah3upG6a4P0s1E55nOrkXrfwtSYoyqUeDdJBD8zaBjL7Y2Ku2c7LQfxncjVgAnbETf_oM-3t1EtTI1YDvj071qFBXntKwAk_T9iVo-QqXV6K1VySXGpvis4P2sIDG9vu1bOcQoVt-v_5-9-jVnzw7YtZauX0fvhtFkcQ7SPaiCjzFo8zBkBGI0-f00xGhyMZk8lb0-_KCHontXkz9HWfTO</recordid><startdate>20130724</startdate><enddate>20130724</enddate><creator>Butin-Israeli, Veronika</creator><creator>Adam, Stephen A</creator><creator>Goldman, Robert D</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130724</creationdate><title>Regulation of nucleotide excision repair by nuclear lamin b1</title><author>Butin-Israeli, Veronika ; Adam, Stephen A ; Goldman, Robert D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-569e0cdf3dc4f94c5a1383f1102fd910f045a0401fbc9078b8f734f433c743ab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Analysis</topic><topic>Apoptosis</topic><topic>Biocompatibility</topic><topic>Biology</topic><topic>Biomedical materials</topic><topic>Cell cycle</topic><topic>Cell Cycle - genetics</topic><topic>Cell Cycle - radiation effects</topic><topic>Cell Cycle Checkpoints - genetics</topic><topic>Cell Cycle Checkpoints - radiation effects</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cellular Senescence - genetics</topic><topic>Cellular Senescence - radiation effects</topic><topic>Damage detection</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA damage</topic><topic>DNA Damage - genetics</topic><topic>DNA Damage - radiation effects</topic><topic>DNA Helicases - genetics</topic><topic>DNA repair</topic><topic>DNA Repair - genetics</topic><topic>DNA Repair - physiology</topic><topic>DNA Repair Enzymes - genetics</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Fibroblasts</topic><topic>Fluorescent Antibody Technique</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Immunoglobulins</topic><topic>Irradiation</topic><topic>Kinases</topic><topic>Lamin Type B - genetics</topic><topic>Lamin Type B - metabolism</topic><topic>Lamins</topic><topic>Molecular biology</topic><topic>Mutation</topic><topic>Nuclei</topic><topic>Nuclei (cytology)</topic><topic>Nucleotide excision repair</topic><topic>Osteosarcoma</topic><topic>Penicillin</topic><topic>Poly-ADP-Ribose Binding Proteins</topic><topic>Proliferating cell nuclear antigen</topic><topic>Proliferating Cell Nuclear Antigen - genetics</topic><topic>Proteins</topic><topic>Radiation damage</topic><topic>Repair</topic><topic>RNA polymerase</topic><topic>Rodents</topic><topic>Senescence</topic><topic>Signaling</topic><topic>Stem cells</topic><topic>Tumor cell lines</topic><topic>Ultraviolet radiation</topic><topic>Ultraviolet Rays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Butin-Israeli, Veronika</creatorcontrib><creatorcontrib>Adam, Stephen A</creatorcontrib><creatorcontrib>Goldman, Robert D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Butin-Israeli, Veronika</au><au>Adam, Stephen A</au><au>Goldman, Robert D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of nucleotide excision repair by nuclear lamin b1</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-07-24</date><risdate>2013</risdate><volume>8</volume><issue>7</issue><spage>e69169</spage><epage>e69169</epage><pages>e69169-e69169</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The nuclear lamins play important roles in the structural organization and function of the metazoan cell nucleus. Recent studies on B-type lamins identified a requirement for lamin B1 (LB1) in the regulation of cell proliferation in normal diploid cells. In order to further investigate the function of LB1 in proliferation, we disrupted its normal expression in U-2 OS human osteosarcoma and other tumor cell lines. Silencing LB1 expression induced G1 cell cycle arrest without significant apoptosis. The arrested cells are unable to mount a timely and effective response to DNA damage induced by UV irradiation. Several proteins involved in the detection and repair of UV damage by the nucleotide excision repair (NER) pathway are down-regulated in LB1 silenced cells including DDB1, CSB and PCNA. We propose that LB1 regulates the DNA damage response to UV irradiation by modulating the expression of specific genes and activating persistent DNA damage signaling. Our findings are relevant to understanding the relationship between the loss of LB1 expression, DNA damage signaling, and replicative senescence.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23894423</pmid><doi>10.1371/journal.pone.0069169</doi><tpages>e69169</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Analysis Apoptosis Biocompatibility Biology Biomedical materials Cell cycle Cell Cycle - genetics Cell Cycle - radiation effects Cell Cycle Checkpoints - genetics Cell Cycle Checkpoints - radiation effects Cell growth Cell Line, Tumor Cell Proliferation Cellular Senescence - genetics Cellular Senescence - radiation effects Damage detection Deoxyribonucleic acid DNA DNA damage DNA Damage - genetics DNA Damage - radiation effects DNA Helicases - genetics DNA repair DNA Repair - genetics DNA Repair - physiology DNA Repair Enzymes - genetics DNA-Binding Proteins - genetics Enzyme-Linked Immunosorbent Assay Fibroblasts Fluorescent Antibody Technique Gene expression Humans Immunoblotting Immunoglobulins Irradiation Kinases Lamin Type B - genetics Lamin Type B - metabolism Lamins Molecular biology Mutation Nuclei Nuclei (cytology) Nucleotide excision repair Osteosarcoma Penicillin Poly-ADP-Ribose Binding Proteins Proliferating cell nuclear antigen Proliferating Cell Nuclear Antigen - genetics Proteins Radiation damage Repair RNA polymerase Rodents Senescence Signaling Stem cells Tumor cell lines Ultraviolet radiation Ultraviolet Rays |
title | Regulation of nucleotide excision repair by nuclear lamin b1 |
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