Genetic dissection of vertebrate 53BP1: A major role in non-homologous end joining of DNA double strand breaks
53BP1 (p53 binding protein) is a BRCT domain-containing protein that is rapidly recruited to DNA double strand breaks (DSBs). To investigate the role of 53BP1 in the DNA damage response, we generated 53BP1 −/− cells from the chicken DT40 cell line. As in mammalian cells, mutation of 53BP1 increased...
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| Veröffentlicht in: | DNA repair 2006-06, Vol.5 (6), p.741-749 |
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| creator | Nakamura, Kyoko Sakai, Wataru Kawamoto, Takuo Bree, Ronan T. Lowndes, Noel F. Takeda, Shunichi Taniguchi, Yoshihito |
| description | 53BP1 (p53 binding protein) is a BRCT domain-containing protein that is rapidly recruited to DNA double strand breaks (DSBs). To investigate the role of 53BP1 in the DNA damage response, we generated
53BP1
−/−
cells from the chicken DT40 cell line. As in mammalian cells, mutation of 53BP1 increased cellular sensitivity to ionizing radiation. Although depletion of 53BP1 resulted in checkpoint defects in mammalian cells, DT40
53BP1
−/−
cells had normal intra S phase and G2/M checkpoints. G1 specific radiosensitivity and a higher sensitivity to topoisomerase II suggested defective non-homologous end joining (NHEJ) defects in DT40
53BP1
−/−
cells. Genetic analyses confirm this suggestion as we have demonstrated an epistatic relationship between
53BP1 and the NHEJ genes,
Ku70 and
Artemis, but not with
Rad54, a gene essential for repair of DSBs by homologous recombination. We conclude that the major role of 53BP1 in supporting survival of DT40 cells that have suffered DNA DSBs is in facilitating repair by NHEJ. |
| doi_str_mv | 10.1016/j.dnarep.2006.03.008 |
| format | Article |
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53BP1
−/−
cells from the chicken DT40 cell line. As in mammalian cells, mutation of 53BP1 increased cellular sensitivity to ionizing radiation. Although depletion of 53BP1 resulted in checkpoint defects in mammalian cells, DT40
53BP1
−/−
cells had normal intra S phase and G2/M checkpoints. G1 specific radiosensitivity and a higher sensitivity to topoisomerase II suggested defective non-homologous end joining (NHEJ) defects in DT40
53BP1
−/−
cells. Genetic analyses confirm this suggestion as we have demonstrated an epistatic relationship between
53BP1 and the NHEJ genes,
Ku70 and
Artemis, but not with
Rad54, a gene essential for repair of DSBs by homologous recombination. We conclude that the major role of 53BP1 in supporting survival of DT40 cells that have suffered DNA DSBs is in facilitating repair by NHEJ.</description><identifier>ISSN: 1568-7864</identifier><identifier>EISSN: 1568-7856</identifier><identifier>DOI: 10.1016/j.dnarep.2006.03.008</identifier><identifier>PMID: 16644291</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>53BP1 ; Animals ; Antigens, Nuclear - biosynthesis ; Artemis ; Bacteriology ; Biological and medical sciences ; Cell Cycle ; Chickens ; DNA - chemistry ; DNA Damage ; DNA Helicases ; DNA Repair ; DNA-Binding Proteins - biosynthesis ; DT40 ; Endonucleases ; Fundamental and applied biological sciences. Psychology ; Genetics ; Growth, nutrition, cell differenciation ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - metabolism ; Ku Autoantigen ; Microbiology ; Molecular and cellular biology ; Molecular genetics ; Mutagenesis. Repair ; Mutation ; Non-homologous end joining ; Nuclear Proteins - biosynthesis ; Protein Structure, Tertiary ; Radiation, Ionizing ; Recombination, Genetic ; Transgenes</subject><ispartof>DNA repair, 2006-06, Vol.5 (6), p.741-749</ispartof><rights>2006 Elsevier B.V.</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c628t-967b237590df97ba6b28b0325f1ca7119a9c4c0971d0e00f3636b92e1ceb096f3</citedby><cites>FETCH-LOGICAL-c628t-967b237590df97ba6b28b0325f1ca7119a9c4c0971d0e00f3636b92e1ceb096f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1568786406000899$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17817108$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16644291$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nakamura, Kyoko</creatorcontrib><creatorcontrib>Sakai, Wataru</creatorcontrib><creatorcontrib>Kawamoto, Takuo</creatorcontrib><creatorcontrib>Bree, Ronan T.</creatorcontrib><creatorcontrib>Lowndes, Noel F.</creatorcontrib><creatorcontrib>Takeda, Shunichi</creatorcontrib><creatorcontrib>Taniguchi, Yoshihito</creatorcontrib><title>Genetic dissection of vertebrate 53BP1: A major role in non-homologous end joining of DNA double strand breaks</title><title>DNA repair</title><addtitle>DNA Repair (Amst)</addtitle><description>53BP1 (p53 binding protein) is a BRCT domain-containing protein that is rapidly recruited to DNA double strand breaks (DSBs). To investigate the role of 53BP1 in the DNA damage response, we generated
53BP1
−/−
cells from the chicken DT40 cell line. As in mammalian cells, mutation of 53BP1 increased cellular sensitivity to ionizing radiation. Although depletion of 53BP1 resulted in checkpoint defects in mammalian cells, DT40
53BP1
−/−
cells had normal intra S phase and G2/M checkpoints. G1 specific radiosensitivity and a higher sensitivity to topoisomerase II suggested defective non-homologous end joining (NHEJ) defects in DT40
53BP1
−/−
cells. Genetic analyses confirm this suggestion as we have demonstrated an epistatic relationship between
53BP1 and the NHEJ genes,
Ku70 and
Artemis, but not with
Rad54, a gene essential for repair of DSBs by homologous recombination. We conclude that the major role of 53BP1 in supporting survival of DT40 cells that have suffered DNA DSBs is in facilitating repair by NHEJ.</description><subject>53BP1</subject><subject>Animals</subject><subject>Antigens, Nuclear - biosynthesis</subject><subject>Artemis</subject><subject>Bacteriology</subject><subject>Biological and medical sciences</subject><subject>Cell Cycle</subject><subject>Chickens</subject><subject>DNA - chemistry</subject><subject>DNA Damage</subject><subject>DNA Helicases</subject><subject>DNA Repair</subject><subject>DNA-Binding Proteins - biosynthesis</subject><subject>DT40</subject><subject>Endonucleases</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetics</subject><subject>Growth, nutrition, cell differenciation</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Ku Autoantigen</subject><subject>Microbiology</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Mutagenesis. Repair</subject><subject>Mutation</subject><subject>Non-homologous end joining</subject><subject>Nuclear Proteins - biosynthesis</subject><subject>Protein Structure, Tertiary</subject><subject>Radiation, Ionizing</subject><subject>Recombination, Genetic</subject><subject>Transgenes</subject><issn>1568-7864</issn><issn>1568-7856</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAQhiMEoqXwBgj5ArekM3FiJxyQlgKlUlU4wNmynUlxSOzFzlbq2-NlV_QGJ4_k7_81mq8oXiJUCCjOp2rwOtK2qgFEBbwC6B4Vp9iKrpRdKx7_nUVzUjxLaQLAVgrxtDhBIZqm7vG08JfkaXWWDS4lsqsLnoWR3VFcyUS9Emv5-6_4lm3YoqcQWQwzMeeZD778EZYwh9uwS4z8wKbgvPO3-_yHmw0bws5kNq1R508TSf9Mz4sno54TvTi-Z8X3Tx-_XXwur79cXl1srksr6m4teyFNzWXbwzD20mhh6s4Ar9sRrZaIve5tY6GXOAABjFxwYfqa0JKBXoz8rHhz6N3G8GtHaVWLS5bmWXvK6yrRAaLo2v-CKGvEmvMMNgfQxpBSpFFto1t0vFcIai9ETeogRO2FKOAqC8mxV8f-nVloeAgdDWTg9RHQyep5zMeyLj1wskOJf4reHTjKZ7tzFFWyjrylwcXsTQ3B_XuT36Fkqe4</recordid><startdate>20060610</startdate><enddate>20060610</enddate><creator>Nakamura, Kyoko</creator><creator>Sakai, Wataru</creator><creator>Kawamoto, Takuo</creator><creator>Bree, Ronan T.</creator><creator>Lowndes, Noel F.</creator><creator>Takeda, Shunichi</creator><creator>Taniguchi, Yoshihito</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><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>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20060610</creationdate><title>Genetic dissection of vertebrate 53BP1: A major role in non-homologous end joining of DNA double strand breaks</title><author>Nakamura, Kyoko ; Sakai, Wataru ; Kawamoto, Takuo ; Bree, Ronan T. ; Lowndes, Noel F. ; Takeda, Shunichi ; Taniguchi, Yoshihito</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c628t-967b237590df97ba6b28b0325f1ca7119a9c4c0971d0e00f3636b92e1ceb096f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>53BP1</topic><topic>Animals</topic><topic>Antigens, Nuclear - biosynthesis</topic><topic>Artemis</topic><topic>Bacteriology</topic><topic>Biological and medical sciences</topic><topic>Cell Cycle</topic><topic>Chickens</topic><topic>DNA - chemistry</topic><topic>DNA Damage</topic><topic>DNA Helicases</topic><topic>DNA Repair</topic><topic>DNA-Binding Proteins - biosynthesis</topic><topic>DT40</topic><topic>Endonucleases</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetics</topic><topic>Growth, nutrition, cell differenciation</topic><topic>Intracellular Signaling Peptides and Proteins - genetics</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Ku Autoantigen</topic><topic>Microbiology</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Mutagenesis. Repair</topic><topic>Mutation</topic><topic>Non-homologous end joining</topic><topic>Nuclear Proteins - biosynthesis</topic><topic>Protein Structure, Tertiary</topic><topic>Radiation, Ionizing</topic><topic>Recombination, Genetic</topic><topic>Transgenes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nakamura, Kyoko</creatorcontrib><creatorcontrib>Sakai, Wataru</creatorcontrib><creatorcontrib>Kawamoto, Takuo</creatorcontrib><creatorcontrib>Bree, Ronan T.</creatorcontrib><creatorcontrib>Lowndes, Noel F.</creatorcontrib><creatorcontrib>Takeda, Shunichi</creatorcontrib><creatorcontrib>Taniguchi, Yoshihito</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>DNA repair</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nakamura, Kyoko</au><au>Sakai, Wataru</au><au>Kawamoto, Takuo</au><au>Bree, Ronan T.</au><au>Lowndes, Noel F.</au><au>Takeda, Shunichi</au><au>Taniguchi, Yoshihito</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic dissection of vertebrate 53BP1: A major role in non-homologous end joining of DNA double strand breaks</atitle><jtitle>DNA repair</jtitle><addtitle>DNA Repair (Amst)</addtitle><date>2006-06-10</date><risdate>2006</risdate><volume>5</volume><issue>6</issue><spage>741</spage><epage>749</epage><pages>741-749</pages><issn>1568-7864</issn><eissn>1568-7856</eissn><abstract>53BP1 (p53 binding protein) is a BRCT domain-containing protein that is rapidly recruited to DNA double strand breaks (DSBs). To investigate the role of 53BP1 in the DNA damage response, we generated
53BP1
−/−
cells from the chicken DT40 cell line. As in mammalian cells, mutation of 53BP1 increased cellular sensitivity to ionizing radiation. Although depletion of 53BP1 resulted in checkpoint defects in mammalian cells, DT40
53BP1
−/−
cells had normal intra S phase and G2/M checkpoints. G1 specific radiosensitivity and a higher sensitivity to topoisomerase II suggested defective non-homologous end joining (NHEJ) defects in DT40
53BP1
−/−
cells. Genetic analyses confirm this suggestion as we have demonstrated an epistatic relationship between
53BP1 and the NHEJ genes,
Ku70 and
Artemis, but not with
Rad54, a gene essential for repair of DSBs by homologous recombination. We conclude that the major role of 53BP1 in supporting survival of DT40 cells that have suffered DNA DSBs is in facilitating repair by NHEJ.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>16644291</pmid><doi>10.1016/j.dnarep.2006.03.008</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | DNA repair, 2006-06, Vol.5 (6), p.741-749 |
| issn | 1568-7864 1568-7856 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68011685 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | 53BP1 Animals Antigens, Nuclear - biosynthesis Artemis Bacteriology Biological and medical sciences Cell Cycle Chickens DNA - chemistry DNA Damage DNA Helicases DNA Repair DNA-Binding Proteins - biosynthesis DT40 Endonucleases Fundamental and applied biological sciences. Psychology Genetics Growth, nutrition, cell differenciation Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism Ku Autoantigen Microbiology Molecular and cellular biology Molecular genetics Mutagenesis. Repair Mutation Non-homologous end joining Nuclear Proteins - biosynthesis Protein Structure, Tertiary Radiation, Ionizing Recombination, Genetic Transgenes |
| title | Genetic dissection of vertebrate 53BP1: A major role in non-homologous end joining of DNA double strand breaks |
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