Genetic interaction between DNA polymerase β and DNA-PKcs in embryogenesis and neurogenesis
DNA polymerase β (Pol β ) has been implicated in base excision repair. Pol β knockout mice exhibit apoptosis in postmitotic neuronal cells and die at birth. Also, mice deficient in nonhomologous end-joining (NHEJ), a major pathway for DNA double-strand break repair, cause massive neuronal apoptosis....
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| Veröffentlicht in: | Cell death and differentiation 2005-02, Vol.12 (2), p.184-191 |
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| creator | Niimi, N Sugo, N Aratani, Y Koyama, H |
| description | DNA polymerase
β
(Pol
β
) has been implicated in base excision repair. Pol
β
knockout mice exhibit apoptosis in postmitotic neuronal cells and die at birth. Also, mice deficient in nonhomologous end-joining (NHEJ), a major pathway for DNA double-strand break repair, cause massive neuronal apoptosis. Severe combined immunodeficiency (SCID) mice have a mutation in the gene encoding DNA-dependent protein kinase catalytic subunit (DNA-PKcs), the component of NHEJ, and exhibit defective lymphogenesis. To study the interaction between Pol
β
and DNA-PKcs, we generated mice doubly deficient in Pol
β
and DNA-PKcs. Pol
β
−/−
DNA-PKcs
scid/scid
embryos displayed greater developmental delay, more extensive neuronal apoptosis, and earlier lethality than Pol
β
−/−
and DNA-PKcs
scid/scid
embryos. Furthermore, to study the involvement of p53 in the phenotype, we generated Pol
β
−/−
DNA-PKcs
scid/scid
p53
−/−
triple-mutant mice. The mutants did not exhibit apoptosis but were lethal with defective neurulation at midgestation. These results suggest a genetic interaction between Pol
β
and DNA-PKcs in embryogenesis and neurogenesis. |
| doi_str_mv | 10.1038/sj.cdd.4401543 |
| format | Article |
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β
(Pol
β
) has been implicated in base excision repair. Pol
β
knockout mice exhibit apoptosis in postmitotic neuronal cells and die at birth. Also, mice deficient in nonhomologous end-joining (NHEJ), a major pathway for DNA double-strand break repair, cause massive neuronal apoptosis. Severe combined immunodeficiency (SCID) mice have a mutation in the gene encoding DNA-dependent protein kinase catalytic subunit (DNA-PKcs), the component of NHEJ, and exhibit defective lymphogenesis. To study the interaction between Pol
β
and DNA-PKcs, we generated mice doubly deficient in Pol
β
and DNA-PKcs. Pol
β
−/−
DNA-PKcs
scid/scid
embryos displayed greater developmental delay, more extensive neuronal apoptosis, and earlier lethality than Pol
β
−/−
and DNA-PKcs
scid/scid
embryos. Furthermore, to study the involvement of p53 in the phenotype, we generated Pol
β
−/−
DNA-PKcs
scid/scid
p53
−/−
triple-mutant mice. The mutants did not exhibit apoptosis but were lethal with defective neurulation at midgestation. These results suggest a genetic interaction between Pol
β
and DNA-PKcs in embryogenesis and neurogenesis.</description><identifier>ISSN: 1350-9047</identifier><identifier>EISSN: 1476-5403</identifier><identifier>DOI: 10.1038/sj.cdd.4401543</identifier><identifier>PMID: 15647757</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Apoptosis ; Apoptosis - genetics ; Apoptosis - physiology ; Biochemistry ; Biomedical and Life Sciences ; Cell Biology ; Cell Cycle Analysis ; Crosses, Genetic ; DNA Polymerase beta - genetics ; DNA Polymerase beta - metabolism ; DNA-Activated Protein Kinase ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Embryo Loss - genetics ; Embryonic Development - genetics ; Embryonic Development - physiology ; Female ; Heterozygote ; Homozygote ; Life Sciences ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Mutant Strains ; Mice, SCID ; Nervous System - embryology ; Nervous System - metabolism ; Nervous System - pathology ; original-paper ; Phenotype ; Protein-Serine-Threonine Kinases - genetics ; Protein-Serine-Threonine Kinases - metabolism ; Stem Cells ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - physiology</subject><ispartof>Cell death and differentiation, 2005-02, Vol.12 (2), p.184-191</ispartof><rights>Springer Nature Limited 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c373t-e22e01b794f6e6bd3476e674f4bed9b1f6bfe1bda529049e2cb437349498462d3</citedby><cites>FETCH-LOGICAL-c373t-e22e01b794f6e6bd3476e674f4bed9b1f6bfe1bda529049e2cb437349498462d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.cdd.4401543$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.cdd.4401543$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15647757$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Niimi, N</creatorcontrib><creatorcontrib>Sugo, N</creatorcontrib><creatorcontrib>Aratani, Y</creatorcontrib><creatorcontrib>Koyama, H</creatorcontrib><title>Genetic interaction between DNA polymerase β and DNA-PKcs in embryogenesis and neurogenesis</title><title>Cell death and differentiation</title><addtitle>Cell Death Differ</addtitle><addtitle>Cell Death Differ</addtitle><description>DNA polymerase
β
(Pol
β
) has been implicated in base excision repair. Pol
β
knockout mice exhibit apoptosis in postmitotic neuronal cells and die at birth. Also, mice deficient in nonhomologous end-joining (NHEJ), a major pathway for DNA double-strand break repair, cause massive neuronal apoptosis. Severe combined immunodeficiency (SCID) mice have a mutation in the gene encoding DNA-dependent protein kinase catalytic subunit (DNA-PKcs), the component of NHEJ, and exhibit defective lymphogenesis. To study the interaction between Pol
β
and DNA-PKcs, we generated mice doubly deficient in Pol
β
and DNA-PKcs. Pol
β
−/−
DNA-PKcs
scid/scid
embryos displayed greater developmental delay, more extensive neuronal apoptosis, and earlier lethality than Pol
β
−/−
and DNA-PKcs
scid/scid
embryos. Furthermore, to study the involvement of p53 in the phenotype, we generated Pol
β
−/−
DNA-PKcs
scid/scid
p53
−/−
triple-mutant mice. The mutants did not exhibit apoptosis but were lethal with defective neurulation at midgestation. These results suggest a genetic interaction between Pol
β
and DNA-PKcs in embryogenesis and neurogenesis.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - genetics</subject><subject>Apoptosis - physiology</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Cell Biology</subject><subject>Cell Cycle Analysis</subject><subject>Crosses, Genetic</subject><subject>DNA Polymerase beta - genetics</subject><subject>DNA Polymerase beta - metabolism</subject><subject>DNA-Activated Protein Kinase</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Embryo Loss - genetics</subject><subject>Embryonic Development - genetics</subject><subject>Embryonic Development - physiology</subject><subject>Female</subject><subject>Heterozygote</subject><subject>Homozygote</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mice, Mutant Strains</subject><subject>Mice, SCID</subject><subject>Nervous System - embryology</subject><subject>Nervous System - metabolism</subject><subject>Nervous System - pathology</subject><subject>original-paper</subject><subject>Phenotype</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Stem Cells</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - physiology</subject><issn>1350-9047</issn><issn>1476-5403</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kLFOwzAYhC0EoqWwMqJMbAl27NjNWBUoiAoYYEOyYvtPlahxip0I9bV4EJ4JlwYxMdn677uT7hA6JzghmE6vfJ1oYxLGMMkYPUBjwgSPM4bpYfjTDMc5ZmKETryvMcZc5PwYjUjGmRCZGKO3BVjoKh1VtgNX6K5qbaSg-wCw0fXjLNq0620TFA_R12dUWLO7xs8P2gdLBI1y23YVMnzlf1QLvfs9nKKjslh7OBveCXq9vXmZ38XLp8X9fLaMNRW0iyFNARMlclZy4MrQUAG4YCVTYHJFSq5KIMoUWRrK5JBqxYKR5SyfMp4aOkGX-9yNa9978J1sKq9hvS4stL2XXNBsKlISwGQPatd676CUG1c1hdtKguVuT-lrGfaUw57BcDEk96oB84cPAwbgag_4INkVOFm3vbOh7X-R3-hbgmw</recordid><startdate>20050201</startdate><enddate>20050201</enddate><creator>Niimi, N</creator><creator>Sugo, N</creator><creator>Aratani, Y</creator><creator>Koyama, H</creator><general>Nature Publishing Group UK</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>7X8</scope></search><sort><creationdate>20050201</creationdate><title>Genetic interaction between DNA polymerase β and DNA-PKcs in embryogenesis and neurogenesis</title><author>Niimi, N ; Sugo, N ; Aratani, Y ; Koyama, H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c373t-e22e01b794f6e6bd3476e674f4bed9b1f6bfe1bda529049e2cb437349498462d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - genetics</topic><topic>Apoptosis - physiology</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Cell Biology</topic><topic>Cell Cycle Analysis</topic><topic>Crosses, Genetic</topic><topic>DNA Polymerase beta - genetics</topic><topic>DNA Polymerase beta - metabolism</topic><topic>DNA-Activated Protein Kinase</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Embryo Loss - genetics</topic><topic>Embryonic Development - genetics</topic><topic>Embryonic Development - physiology</topic><topic>Female</topic><topic>Heterozygote</topic><topic>Homozygote</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mice, Mutant Strains</topic><topic>Mice, SCID</topic><topic>Nervous System - embryology</topic><topic>Nervous System - metabolism</topic><topic>Nervous System - pathology</topic><topic>original-paper</topic><topic>Phenotype</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Stem Cells</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Niimi, N</creatorcontrib><creatorcontrib>Sugo, N</creatorcontrib><creatorcontrib>Aratani, Y</creatorcontrib><creatorcontrib>Koyama, H</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cell death and differentiation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Niimi, N</au><au>Sugo, N</au><au>Aratani, Y</au><au>Koyama, H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic interaction between DNA polymerase β and DNA-PKcs in embryogenesis and neurogenesis</atitle><jtitle>Cell death and differentiation</jtitle><stitle>Cell Death Differ</stitle><addtitle>Cell Death Differ</addtitle><date>2005-02-01</date><risdate>2005</risdate><volume>12</volume><issue>2</issue><spage>184</spage><epage>191</epage><pages>184-191</pages><issn>1350-9047</issn><eissn>1476-5403</eissn><abstract>DNA polymerase
β
(Pol
β
) has been implicated in base excision repair. Pol
β
knockout mice exhibit apoptosis in postmitotic neuronal cells and die at birth. Also, mice deficient in nonhomologous end-joining (NHEJ), a major pathway for DNA double-strand break repair, cause massive neuronal apoptosis. Severe combined immunodeficiency (SCID) mice have a mutation in the gene encoding DNA-dependent protein kinase catalytic subunit (DNA-PKcs), the component of NHEJ, and exhibit defective lymphogenesis. To study the interaction between Pol
β
and DNA-PKcs, we generated mice doubly deficient in Pol
β
and DNA-PKcs. Pol
β
−/−
DNA-PKcs
scid/scid
embryos displayed greater developmental delay, more extensive neuronal apoptosis, and earlier lethality than Pol
β
−/−
and DNA-PKcs
scid/scid
embryos. Furthermore, to study the involvement of p53 in the phenotype, we generated Pol
β
−/−
DNA-PKcs
scid/scid
p53
−/−
triple-mutant mice. The mutants did not exhibit apoptosis but were lethal with defective neurulation at midgestation. These results suggest a genetic interaction between Pol
β
and DNA-PKcs in embryogenesis and neurogenesis.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>15647757</pmid><doi>10.1038/sj.cdd.4401543</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Springer Online Journals Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Apoptosis Apoptosis - genetics Apoptosis - physiology Biochemistry Biomedical and Life Sciences Cell Biology Cell Cycle Analysis Crosses, Genetic DNA Polymerase beta - genetics DNA Polymerase beta - metabolism DNA-Activated Protein Kinase DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Embryo Loss - genetics Embryonic Development - genetics Embryonic Development - physiology Female Heterozygote Homozygote Life Sciences Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Mutant Strains Mice, SCID Nervous System - embryology Nervous System - metabolism Nervous System - pathology original-paper Phenotype Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Stem Cells Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - physiology |
| title | Genetic interaction between DNA polymerase β and DNA-PKcs in embryogenesis and neurogenesis |
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