SMC1 coordinates DNA double-strand break repair pathways
The SMC1/SMC3 heterodimer acts in sister chromatid cohesion, and recent data indicate a function in DNA double-strand break repair (DSBR). Since this role of SMC proteins has remained largely elusive, we explored interactions between SMC1 and the homologous recombination (HR) or non-homologous end-j...
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| Veröffentlicht in: | Nucleic acids research 2004-01, Vol.32 (13), p.3921-3929 |
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| creator | Schär, Primo Fäsi, Margaret Jessberger, Rolf |
| description | The SMC1/SMC3 heterodimer acts in sister chromatid cohesion, and recent data indicate a function in DNA double-strand break repair (DSBR). Since this role of SMC proteins has remained largely elusive, we explored interactions between SMC1 and the homologous recombination (HR) or non-homologous end-joining (NHEJ) pathways for DSBR in Saccharomyces cerevisiae. Analysis of conditional single- and double mutants of smc1-2 with rad52Δ, rad54Δ, rad50Δ or dnl4Δ illustrates a significant contribution of SMC1 to the overall capacity of cells to repair DSBs. smc1 but not smc2 mutants show increased hypersensitivity of HR mutants to ionizing irradiation and to the DNA crosslinking agent cis-platin. Haploid, but not diploid smc1-2 mutants were severely affected in repairing multiple genomic DNA breaks, suggesting a selective role of SMC1 in sister chromatid recombination. smc1-2 mutants were also 15-fold less efficient and highly error-prone in plasmid end-joining through the NHEJ pathway. Strikingly, inactivation of RAD52 or RAD54 fully rescued efficiency and accuracy of NHEJ in the smc1 background. Therefore, we propose coordination of HR and NHEJ processes by Smc1p through interaction with the RAD52 pathway. |
| doi_str_mv | 10.1093/nar/gkh716 |
| format | Article |
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Since this role of SMC proteins has remained largely elusive, we explored interactions between SMC1 and the homologous recombination (HR) or non-homologous end-joining (NHEJ) pathways for DSBR in Saccharomyces cerevisiae. Analysis of conditional single- and double mutants of smc1-2 with rad52Δ, rad54Δ, rad50Δ or dnl4Δ illustrates a significant contribution of SMC1 to the overall capacity of cells to repair DSBs. smc1 but not smc2 mutants show increased hypersensitivity of HR mutants to ionizing irradiation and to the DNA crosslinking agent cis-platin. Haploid, but not diploid smc1-2 mutants were severely affected in repairing multiple genomic DNA breaks, suggesting a selective role of SMC1 in sister chromatid recombination. smc1-2 mutants were also 15-fold less efficient and highly error-prone in plasmid end-joining through the NHEJ pathway. Strikingly, inactivation of RAD52 or RAD54 fully rescued efficiency and accuracy of NHEJ in the smc1 background. Therefore, we propose coordination of HR and NHEJ processes by Smc1p through interaction with the RAD52 pathway.</description><identifier>ISSN: 0305-1048</identifier><identifier>ISSN: 1362-4962</identifier><identifier>EISSN: 1362-4962</identifier><identifier>DOI: 10.1093/nar/gkh716</identifier><identifier>PMID: 15280507</identifier><identifier>CODEN: NARHAD</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Base Sequence ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - physiology ; Chromosomal Proteins, Non-Histone - genetics ; Chromosomal Proteins, Non-Histone - physiology ; Cisplatin - toxicity ; Cross-Linking Reagents - toxicity ; DNA Damage ; DNA Repair ; Molecular Sequence Data ; Mutation ; Radiation, Ionizing ; Recombination, Genetic ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae - drug effects ; Saccharomyces cerevisiae - genetics ; Saccharomyces cerevisiae Proteins - genetics ; Saccharomyces cerevisiae Proteins - physiology ; Signal Transduction ; Telomere - chemistry</subject><ispartof>Nucleic acids research, 2004-01, Vol.32 (13), p.3921-3929</ispartof><rights>Copyright Oxford University Press(England) 2004</rights><rights>Copyright © 2004 Oxford University Press 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500t-72d4e16af0bcb51eabfc3e5a393d0d34585ec971dab5340cf5a6c3b81dfdf4f53</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC506803/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC506803/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15280507$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schär, Primo</creatorcontrib><creatorcontrib>Fäsi, Margaret</creatorcontrib><creatorcontrib>Jessberger, Rolf</creatorcontrib><title>SMC1 coordinates DNA double-strand break repair pathways</title><title>Nucleic acids research</title><addtitle>Nucl. Acids Res</addtitle><description>The SMC1/SMC3 heterodimer acts in sister chromatid cohesion, and recent data indicate a function in DNA double-strand break repair (DSBR). Since this role of SMC proteins has remained largely elusive, we explored interactions between SMC1 and the homologous recombination (HR) or non-homologous end-joining (NHEJ) pathways for DSBR in Saccharomyces cerevisiae. Analysis of conditional single- and double mutants of smc1-2 with rad52Δ, rad54Δ, rad50Δ or dnl4Δ illustrates a significant contribution of SMC1 to the overall capacity of cells to repair DSBs. smc1 but not smc2 mutants show increased hypersensitivity of HR mutants to ionizing irradiation and to the DNA crosslinking agent cis-platin. Haploid, but not diploid smc1-2 mutants were severely affected in repairing multiple genomic DNA breaks, suggesting a selective role of SMC1 in sister chromatid recombination. smc1-2 mutants were also 15-fold less efficient and highly error-prone in plasmid end-joining through the NHEJ pathway. Strikingly, inactivation of RAD52 or RAD54 fully rescued efficiency and accuracy of NHEJ in the smc1 background. Therefore, we propose coordination of HR and NHEJ processes by Smc1p through interaction with the RAD52 pathway.</description><subject>Base Sequence</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - physiology</subject><subject>Chromosomal Proteins, Non-Histone - genetics</subject><subject>Chromosomal Proteins, Non-Histone - physiology</subject><subject>Cisplatin - toxicity</subject><subject>Cross-Linking Reagents - toxicity</subject><subject>DNA Damage</subject><subject>DNA Repair</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Radiation, Ionizing</subject><subject>Recombination, Genetic</subject><subject>Saccharomyces cerevisiae</subject><subject>Saccharomyces cerevisiae - drug effects</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Saccharomyces cerevisiae Proteins - genetics</subject><subject>Saccharomyces cerevisiae Proteins - physiology</subject><subject>Signal Transduction</subject><subject>Telomere - chemistry</subject><issn>0305-1048</issn><issn>1362-4962</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0U1v1DAQBmALUdFt4cIPQBEHDpXSjj_Gdg4cqgXaSgscgAr1Yjm20003Gy92AvTfN9WuyscFTj7MM6PxvIQ8p3BMoeInvU0n16ulovIRmVEuWSkqyR6TGXDAkoLQ--Qg5xsAKiiKJ2SfItOAoGZEf3o_p4WLMfm2t0PIxZsPp4WPY92FMg_J9r6oU7CrIoWNbVOxscPyh73NT8leY7scnu3eQ_Ll3dvP8_Ny8fHsYn66KB0CDKViXgQqbQO1q5EGWzeOB7S84h48F6gxuEpRb2vkAlyDVjpea-ob34gG-SF5vZ27Get18C7001Kd2aR2bdOtibY1f1b6dmmu43eDIDXwqf_Vrj_Fb2PIg1m32YWus32IYzZSKuRKiH9CWmmlgdH_gFJWTN3Dl3_BmzimfrqWYQASK2ByQkdb5FLMOYXm4WsUzH28ZorXbOOd8Ivfj_GL7vKcQLkFbR7Cz4e6TSsjFVdozr9emTN2iQt9dWkqfgcwtLCg</recordid><startdate>20040101</startdate><enddate>20040101</enddate><creator>Schär, Primo</creator><creator>Fäsi, Margaret</creator><creator>Jessberger, Rolf</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</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>7QL</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20040101</creationdate><title>SMC1 coordinates DNA double-strand break repair pathways</title><author>Schär, Primo ; Fäsi, Margaret ; Jessberger, Rolf</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c500t-72d4e16af0bcb51eabfc3e5a393d0d34585ec971dab5340cf5a6c3b81dfdf4f53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Base Sequence</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - physiology</topic><topic>Chromosomal Proteins, Non-Histone - genetics</topic><topic>Chromosomal Proteins, Non-Histone - physiology</topic><topic>Cisplatin - toxicity</topic><topic>Cross-Linking Reagents - toxicity</topic><topic>DNA Damage</topic><topic>DNA Repair</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Radiation, Ionizing</topic><topic>Recombination, Genetic</topic><topic>Saccharomyces cerevisiae</topic><topic>Saccharomyces cerevisiae - drug effects</topic><topic>Saccharomyces cerevisiae - genetics</topic><topic>Saccharomyces cerevisiae Proteins - genetics</topic><topic>Saccharomyces cerevisiae Proteins - physiology</topic><topic>Signal Transduction</topic><topic>Telomere - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schär, Primo</creatorcontrib><creatorcontrib>Fäsi, Margaret</creatorcontrib><creatorcontrib>Jessberger, Rolf</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schär, Primo</au><au>Fäsi, Margaret</au><au>Jessberger, Rolf</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SMC1 coordinates DNA double-strand break repair pathways</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucl. Acids Res</addtitle><date>2004-01-01</date><risdate>2004</risdate><volume>32</volume><issue>13</issue><spage>3921</spage><epage>3929</epage><pages>3921-3929</pages><issn>0305-1048</issn><issn>1362-4962</issn><eissn>1362-4962</eissn><coden>NARHAD</coden><abstract>The SMC1/SMC3 heterodimer acts in sister chromatid cohesion, and recent data indicate a function in DNA double-strand break repair (DSBR). Since this role of SMC proteins has remained largely elusive, we explored interactions between SMC1 and the homologous recombination (HR) or non-homologous end-joining (NHEJ) pathways for DSBR in Saccharomyces cerevisiae. Analysis of conditional single- and double mutants of smc1-2 with rad52Δ, rad54Δ, rad50Δ or dnl4Δ illustrates a significant contribution of SMC1 to the overall capacity of cells to repair DSBs. smc1 but not smc2 mutants show increased hypersensitivity of HR mutants to ionizing irradiation and to the DNA crosslinking agent cis-platin. Haploid, but not diploid smc1-2 mutants were severely affected in repairing multiple genomic DNA breaks, suggesting a selective role of SMC1 in sister chromatid recombination. smc1-2 mutants were also 15-fold less efficient and highly error-prone in plasmid end-joining through the NHEJ pathway. Strikingly, inactivation of RAD52 or RAD54 fully rescued efficiency and accuracy of NHEJ in the smc1 background. Therefore, we propose coordination of HR and NHEJ processes by Smc1p through interaction with the RAD52 pathway.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>15280507</pmid><doi>10.1093/nar/gkh716</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Base Sequence Cell Cycle Proteins - genetics Cell Cycle Proteins - physiology Chromosomal Proteins, Non-Histone - genetics Chromosomal Proteins, Non-Histone - physiology Cisplatin - toxicity Cross-Linking Reagents - toxicity DNA Damage DNA Repair Molecular Sequence Data Mutation Radiation, Ionizing Recombination, Genetic Saccharomyces cerevisiae Saccharomyces cerevisiae - drug effects Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae Proteins - genetics Saccharomyces cerevisiae Proteins - physiology Signal Transduction Telomere - chemistry |
| title | SMC1 coordinates DNA double-strand break repair pathways |
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