new connection of mRNP biogenesis and export with transcription-coupled repair
Although DNA repair is faster in the transcribed strand of active genes, little is known about the possible contribution of mRNP biogenesis and export in transcription-coupled repair (TCR). Interestingly, mutants of THO, a transcription complex involved in maintenance of genome integrity, mRNP bioge...
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| Veröffentlicht in: | Nucleic acids research 2007-06, Vol.35 (12), p.3893-3906 |
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| creator | Gaillard, Hélène Wellinger, Ralf Erik Aguilera, Andrés |
| description | Although DNA repair is faster in the transcribed strand of active genes, little is known about the possible contribution of mRNP biogenesis and export in transcription-coupled repair (TCR). Interestingly, mutants of THO, a transcription complex involved in maintenance of genome integrity, mRNP biogenesis and export, were recently found to be deficient in nucleotide excision repair. In this study we show by molecular DNA repair analysis, that Sub2-Yra1 and Thp1-Sac3, two main mRNA export complexes, are required for efficient TCR in yeast. Careful analysis revealed that THO mutants are also specifically affected in TCR. Ribozyme-mediated mRNA self-cleavage between two hot spots for UV damage showed that efficient TCR does not depend on the nascent mRNA, neither in wild-type nor in mutant cells. Along with severe UV damage-dependent loss in processivity, RNAPII was found binding to chromatin upon UV irradiation in THO mutants, suggesting that RNAPII remains stalled at DNA lesions. Furthermore, Def1, a factor responsible for the degradation of stalled RNAPII, appears essential for the viability of THO mutants subjected to DNA damage. Our results indicate that RNAPII is not proficient for TCR in mRNP biogenesis and export mutants, opening new perspectives on our knowledge of TCR in eukaryotic cells. |
| doi_str_mv | 10.1093/nar/gkm373 |
| format | Article |
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Interestingly, mutants of THO, a transcription complex involved in maintenance of genome integrity, mRNP biogenesis and export, were recently found to be deficient in nucleotide excision repair. In this study we show by molecular DNA repair analysis, that Sub2-Yra1 and Thp1-Sac3, two main mRNA export complexes, are required for efficient TCR in yeast. Careful analysis revealed that THO mutants are also specifically affected in TCR. Ribozyme-mediated mRNA self-cleavage between two hot spots for UV damage showed that efficient TCR does not depend on the nascent mRNA, neither in wild-type nor in mutant cells. Along with severe UV damage-dependent loss in processivity, RNAPII was found binding to chromatin upon UV irradiation in THO mutants, suggesting that RNAPII remains stalled at DNA lesions. Furthermore, Def1, a factor responsible for the degradation of stalled RNAPII, appears essential for the viability of THO mutants subjected to DNA damage. 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Interestingly, mutants of THO, a transcription complex involved in maintenance of genome integrity, mRNP biogenesis and export, were recently found to be deficient in nucleotide excision repair. In this study we show by molecular DNA repair analysis, that Sub2-Yra1 and Thp1-Sac3, two main mRNA export complexes, are required for efficient TCR in yeast. Careful analysis revealed that THO mutants are also specifically affected in TCR. Ribozyme-mediated mRNA self-cleavage between two hot spots for UV damage showed that efficient TCR does not depend on the nascent mRNA, neither in wild-type nor in mutant cells. Along with severe UV damage-dependent loss in processivity, RNAPII was found binding to chromatin upon UV irradiation in THO mutants, suggesting that RNAPII remains stalled at DNA lesions. Furthermore, Def1, a factor responsible for the degradation of stalled RNAPII, appears essential for the viability of THO mutants subjected to DNA damage. Our results indicate that RNAPII is not proficient for TCR in mRNP biogenesis and export mutants, opening new perspectives on our knowledge of TCR in eukaryotic cells.</description><subject>Active Transport, Cell Nucleus</subject><subject>Cell Nucleus - metabolism</subject><subject>Chromosomal Proteins, Non-Histone - physiology</subject><subject>DNA Damage</subject><subject>DNA Repair</subject><subject>Gene Deletion</subject><subject>Genes, Fungal</subject><subject>Genome, Fungal</subject><subject>Models, Genetic</subject><subject>Molecular Biology</subject><subject>Ribonucleoproteins - metabolism</subject><subject>RNA Polymerase II - metabolism</subject><subject>RNA, Messenger - metabolism</subject><subject>Saccharomyces cerevisiae Proteins - physiology</subject><subject>Transcription Factors - genetics</subject><subject>Transcription, Genetic</subject><subject>Ultraviolet Rays</subject><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0U1rFTEUBuAgir2tbvwBGgRdCGNPJt8bQUr9gFJF7TrkZjK3qTPJmMxY_femzMWvha6yyJOXk_Mi9IDAcwKaHkebj3efRyrpLbQhVLQN06K9jTZAgTcEmDpAh6VcARBGOLuLDojkVCoiNug8-mvsUozezSFFnHo8fjh_j7ch7Xz0JRRsY4f9tynlGV-H-RLP2cbicphuHjQuLdPgO5z9ZEO-h-70dij-_v48QhevTj-dvGnO3r1-e_LyrHFMqbnplJC8J1b4TmtPKHeWbm1rHVBpCZN6qxytw0NPVQeCE8Z413GniadQDT1CL9bcadmOvnM-1qkGM-Uw2vzdJBvMnzcxXJpd-mqIJprptgY83Qfk9GXxZTZjKM4Pg40-LcVIEFqBpP-FLbRCccoqfPwXvEpLjnUL1YBomWK8omcrcjmVkn3_c2QC5qZMU8s0a5kVP_z9k7_ovr0KnqygdvDvoEer620ydpdDMRcfWyB1l1JpCZz-ADAOsYk</recordid><startdate>20070601</startdate><enddate>20070601</enddate><creator>Gaillard, Hélène</creator><creator>Wellinger, Ralf Erik</creator><creator>Aguilera, Andrés</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>FBQ</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>20070601</creationdate><title>new connection of mRNP biogenesis and export with transcription-coupled repair</title><author>Gaillard, Hélène ; 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Interestingly, mutants of THO, a transcription complex involved in maintenance of genome integrity, mRNP biogenesis and export, were recently found to be deficient in nucleotide excision repair. In this study we show by molecular DNA repair analysis, that Sub2-Yra1 and Thp1-Sac3, two main mRNA export complexes, are required for efficient TCR in yeast. Careful analysis revealed that THO mutants are also specifically affected in TCR. Ribozyme-mediated mRNA self-cleavage between two hot spots for UV damage showed that efficient TCR does not depend on the nascent mRNA, neither in wild-type nor in mutant cells. Along with severe UV damage-dependent loss in processivity, RNAPII was found binding to chromatin upon UV irradiation in THO mutants, suggesting that RNAPII remains stalled at DNA lesions. Furthermore, Def1, a factor responsible for the degradation of stalled RNAPII, appears essential for the viability of THO mutants subjected to DNA damage. 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| source | Oxford Open Access Journals |
| subjects | Active Transport, Cell Nucleus Cell Nucleus - metabolism Chromosomal Proteins, Non-Histone - physiology DNA Damage DNA Repair Gene Deletion Genes, Fungal Genome, Fungal Models, Genetic Molecular Biology Ribonucleoproteins - metabolism RNA Polymerase II - metabolism RNA, Messenger - metabolism Saccharomyces cerevisiae Proteins - physiology Transcription Factors - genetics Transcription, Genetic Ultraviolet Rays |
| title | new connection of mRNP biogenesis and export with transcription-coupled repair |
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