Ku70 is required for DNA repair but not for T cell antigen receptor gene recombination In vivo
Ku is a complex of two proteins, Ku70 and Ku80, and functions as a heterodimer to bind DNA double-strand breaks (DSB) and activate DNA-dependent protein kinase. The role of the Ku70 subunit in DNA DSB repair, hypersensitivity to ionizing radiation, and V(D)J recombination was examined in mice that l...
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| Veröffentlicht in: | The Journal of experimental medicine 1997-09, Vol.186 (6), p.921-929 |
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| container_title | The Journal of experimental medicine |
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| creator | Ouyang, H Nussenzweig, A Kurimasa, A Soares, V C Li, X Cordon-Cardo, C Li, W h Cheong, N Nussenzweig, M Iliakis, G Chen, D J Li, G C |
| description | Ku is a complex of two proteins, Ku70 and Ku80, and functions as a heterodimer to bind DNA double-strand breaks (DSB) and activate DNA-dependent protein kinase. The role of the Ku70 subunit in DNA DSB repair, hypersensitivity to ionizing radiation, and V(D)J recombination was examined in mice that lack Ku70 (Ku70(-/-)). Like Ku80(-/-) mice, Ku70(-/-) mice showed a profound deficiency in DNA DSB repair and were proportional dwarfs. Surprisingly, in contrast to Ku80(-/-) mice in which both T and B lymphocyte development were arrested at an early stage, lack of Ku70 was compatible with T cell receptor gene recombination and the development of mature CD4+CD8- and CD4-CD8+ T cells. Our data shows, for the first time, that Ku70 plays an essential role in DNA DSB repair, but is not required for TCR V(D)J recombination. These results suggest that distinct but overlapping repair pathways may mediate DNA DSB repair and V(D)J recombination. |
| doi_str_mv | 10.1084/jem.186.6.921 |
| format | Article |
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The role of the Ku70 subunit in DNA DSB repair, hypersensitivity to ionizing radiation, and V(D)J recombination was examined in mice that lack Ku70 (Ku70(-/-)). Like Ku80(-/-) mice, Ku70(-/-) mice showed a profound deficiency in DNA DSB repair and were proportional dwarfs. Surprisingly, in contrast to Ku80(-/-) mice in which both T and B lymphocyte development were arrested at an early stage, lack of Ku70 was compatible with T cell receptor gene recombination and the development of mature CD4+CD8- and CD4-CD8+ T cells. Our data shows, for the first time, that Ku70 plays an essential role in DNA DSB repair, but is not required for TCR V(D)J recombination. These results suggest that distinct but overlapping repair pathways may mediate DNA DSB repair and V(D)J recombination.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.186.6.921</identifier><identifier>PMID: 9294146</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Animals ; Antigens, Nuclear ; B-Lymphocytes - cytology ; B-Lymphocytes - immunology ; B-Lymphocytes - metabolism ; Base Sequence ; BASIC BIOLOGICAL SCIENCES ; Cell Differentiation ; DNA - genetics ; DNA Helicases ; DNA Primers - genetics ; DNA Repair - genetics ; DNA Repair - physiology ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Gene Rearrangement, T-Lymphocyte ; Gene Targeting ; Immunology ; Ku Autoantigen ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Polymerase Chain Reaction ; Receptors, Antigen, T-Cell - genetics ; Recombination, Genetic ; Research & Experimental Medicine ; T-Lymphocytes - cytology ; T-Lymphocytes - immunology ; T-Lymphocytes - metabolism</subject><ispartof>The Journal of experimental medicine, 1997-09, Vol.186 (6), p.921-929</ispartof><rights>1997</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-c4ff3d24ff561af49a021f6c25f2e63635958d49abd68f3d35ec41c57cf77f7f3</citedby><cites>FETCH-LOGICAL-c440t-c4ff3d24ff561af49a021f6c25f2e63635958d49abd68f3d35ec41c57cf77f7f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9294146$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/servlets/purl/1625177$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Ouyang, H</creatorcontrib><creatorcontrib>Nussenzweig, A</creatorcontrib><creatorcontrib>Kurimasa, A</creatorcontrib><creatorcontrib>Soares, V C</creatorcontrib><creatorcontrib>Li, X</creatorcontrib><creatorcontrib>Cordon-Cardo, C</creatorcontrib><creatorcontrib>Li, W h</creatorcontrib><creatorcontrib>Cheong, N</creatorcontrib><creatorcontrib>Nussenzweig, M</creatorcontrib><creatorcontrib>Iliakis, G</creatorcontrib><creatorcontrib>Chen, D J</creatorcontrib><creatorcontrib>Li, G C</creatorcontrib><creatorcontrib>Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)</creatorcontrib><title>Ku70 is required for DNA repair but not for T cell antigen receptor gene recombination In vivo</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>Ku is a complex of two proteins, Ku70 and Ku80, and functions as a heterodimer to bind DNA double-strand breaks (DSB) and activate DNA-dependent protein kinase. The role of the Ku70 subunit in DNA DSB repair, hypersensitivity to ionizing radiation, and V(D)J recombination was examined in mice that lack Ku70 (Ku70(-/-)). Like Ku80(-/-) mice, Ku70(-/-) mice showed a profound deficiency in DNA DSB repair and were proportional dwarfs. Surprisingly, in contrast to Ku80(-/-) mice in which both T and B lymphocyte development were arrested at an early stage, lack of Ku70 was compatible with T cell receptor gene recombination and the development of mature CD4+CD8- and CD4-CD8+ T cells. Our data shows, for the first time, that Ku70 plays an essential role in DNA DSB repair, but is not required for TCR V(D)J recombination. These results suggest that distinct but overlapping repair pathways may mediate DNA DSB repair and V(D)J recombination.</description><subject>Animals</subject><subject>Antigens, Nuclear</subject><subject>B-Lymphocytes - cytology</subject><subject>B-Lymphocytes - immunology</subject><subject>B-Lymphocytes - metabolism</subject><subject>Base Sequence</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>Cell Differentiation</subject><subject>DNA - genetics</subject><subject>DNA Helicases</subject><subject>DNA Primers - genetics</subject><subject>DNA Repair - genetics</subject><subject>DNA Repair - physiology</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Gene Rearrangement, T-Lymphocyte</subject><subject>Gene Targeting</subject><subject>Immunology</subject><subject>Ku Autoantigen</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Molecular Sequence Data</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Polymerase Chain Reaction</subject><subject>Receptors, Antigen, T-Cell - genetics</subject><subject>Recombination, Genetic</subject><subject>Research & Experimental Medicine</subject><subject>T-Lymphocytes - cytology</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - metabolism</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkTtPHDEUha0IBAtJmTKSRZFuNn573CAhCA8FQUPaWF6PDUY79mJ7VuLfx8uuUKjS3Kt77qfjxwHgK0ZzjHr249mNc9yLuZgrgj-BGeYMdYrTfg_MECKkwwjJQ3BUyjNCmDEuDsCBIophJmbgz69JIhgKzO5lCtkN0KcML-7OmrAyIcPFVGFM9U1-gNYtl9DEGh5dbIR1q9r0NrjNlMZFiKaGFOFNhOuwTp_BvjfL4r7s-jH4ffnz4fy6u72_ujk_u-0sY6i26j0dSKtcYOOZMohgLyzhnjhBBeWK90OTF4PoG0m5swxbLq2X0ktPj8Hp1nc1LUY3WBdrNku9ymE0-VUnE_THTQxP-jGtNcFKIS6bwcnWIJUadLGhOvtkU4zOVo0F4VhuoO-7U3J6mVypegxl8yUmujQVLRWRiir1X7AZCiYkbWC3BW1OpWTn36-Mkd7Eq1u8usWrhW7xNv7bv-98p3d50r_CP6E0</recordid><startdate>19970915</startdate><enddate>19970915</enddate><creator>Ouyang, H</creator><creator>Nussenzweig, A</creator><creator>Kurimasa, A</creator><creator>Soares, V C</creator><creator>Li, X</creator><creator>Cordon-Cardo, C</creator><creator>Li, W h</creator><creator>Cheong, N</creator><creator>Nussenzweig, M</creator><creator>Iliakis, G</creator><creator>Chen, D J</creator><creator>Li, G C</creator><general>Rockefeller University Press</general><general>The Rockefeller University Press</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>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>OIOZB</scope><scope>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>19970915</creationdate><title>Ku70 is required for DNA repair but not for T cell antigen receptor gene recombination In vivo</title><author>Ouyang, H ; Nussenzweig, A ; Kurimasa, A ; Soares, V C ; Li, X ; Cordon-Cardo, C ; Li, W h ; Cheong, N ; Nussenzweig, M ; Iliakis, G ; Chen, D J ; Li, G C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-c4ff3d24ff561af49a021f6c25f2e63635958d49abd68f3d35ec41c57cf77f7f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Animals</topic><topic>Antigens, Nuclear</topic><topic>B-Lymphocytes - cytology</topic><topic>B-Lymphocytes - immunology</topic><topic>B-Lymphocytes - metabolism</topic><topic>Base Sequence</topic><topic>BASIC BIOLOGICAL SCIENCES</topic><topic>Cell Differentiation</topic><topic>DNA - genetics</topic><topic>DNA Helicases</topic><topic>DNA Primers - genetics</topic><topic>DNA Repair - genetics</topic><topic>DNA Repair - physiology</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Gene Rearrangement, T-Lymphocyte</topic><topic>Gene Targeting</topic><topic>Immunology</topic><topic>Ku Autoantigen</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Molecular Sequence Data</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Polymerase Chain Reaction</topic><topic>Receptors, Antigen, T-Cell - genetics</topic><topic>Recombination, Genetic</topic><topic>Research & Experimental Medicine</topic><topic>T-Lymphocytes - cytology</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ouyang, H</creatorcontrib><creatorcontrib>Nussenzweig, A</creatorcontrib><creatorcontrib>Kurimasa, A</creatorcontrib><creatorcontrib>Soares, V C</creatorcontrib><creatorcontrib>Li, X</creatorcontrib><creatorcontrib>Cordon-Cardo, C</creatorcontrib><creatorcontrib>Li, W h</creatorcontrib><creatorcontrib>Cheong, N</creatorcontrib><creatorcontrib>Nussenzweig, M</creatorcontrib><creatorcontrib>Iliakis, G</creatorcontrib><creatorcontrib>Chen, D J</creatorcontrib><creatorcontrib>Li, G C</creatorcontrib><creatorcontrib>Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV - Hybrid</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ouyang, H</au><au>Nussenzweig, A</au><au>Kurimasa, A</au><au>Soares, V C</au><au>Li, X</au><au>Cordon-Cardo, C</au><au>Li, W h</au><au>Cheong, N</au><au>Nussenzweig, M</au><au>Iliakis, G</au><au>Chen, D J</au><au>Li, G C</au><aucorp>Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ku70 is required for DNA repair but not for T cell antigen receptor gene recombination In vivo</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>1997-09-15</date><risdate>1997</risdate><volume>186</volume><issue>6</issue><spage>921</spage><epage>929</epage><pages>921-929</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><abstract>Ku is a complex of two proteins, Ku70 and Ku80, and functions as a heterodimer to bind DNA double-strand breaks (DSB) and activate DNA-dependent protein kinase. The role of the Ku70 subunit in DNA DSB repair, hypersensitivity to ionizing radiation, and V(D)J recombination was examined in mice that lack Ku70 (Ku70(-/-)). Like Ku80(-/-) mice, Ku70(-/-) mice showed a profound deficiency in DNA DSB repair and were proportional dwarfs. Surprisingly, in contrast to Ku80(-/-) mice in which both T and B lymphocyte development were arrested at an early stage, lack of Ku70 was compatible with T cell receptor gene recombination and the development of mature CD4+CD8- and CD4-CD8+ T cells. Our data shows, for the first time, that Ku70 plays an essential role in DNA DSB repair, but is not required for TCR V(D)J recombination. These results suggest that distinct but overlapping repair pathways may mediate DNA DSB repair and V(D)J recombination.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>9294146</pmid><doi>10.1084/jem.186.6.921</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antigens, Nuclear B-Lymphocytes - cytology B-Lymphocytes - immunology B-Lymphocytes - metabolism Base Sequence BASIC BIOLOGICAL SCIENCES Cell Differentiation DNA - genetics DNA Helicases DNA Primers - genetics DNA Repair - genetics DNA Repair - physiology DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Gene Rearrangement, T-Lymphocyte Gene Targeting Immunology Ku Autoantigen Mice Mice, Knockout Molecular Sequence Data Nuclear Proteins - genetics Nuclear Proteins - metabolism Polymerase Chain Reaction Receptors, Antigen, T-Cell - genetics Recombination, Genetic Research & Experimental Medicine T-Lymphocytes - cytology T-Lymphocytes - immunology T-Lymphocytes - metabolism |
| title | Ku70 is required for DNA repair but not for T cell antigen receptor gene recombination In vivo |
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