Major Roles for Pyrimidine Dimers, Nucleotide Excision Repair, and ATR in the Alternative Splicing Response to UV Irradiation
We have previously found that UV irradiation promotes RNA polymerase II (RNAPII) hyperphosphorylation and subsequent changes in alternative splicing (AS). We show now that UV-induced DNA damage is not only necessary but sufficient to trigger the AS response and that photolyase-mediated removal of th...
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todo:paper_22111247_v18_n12_p2868_Munoz2023-10-03T16:40:30Z Major Roles for Pyrimidine Dimers, Nucleotide Excision Repair, and ATR in the Alternative Splicing Response to UV Irradiation Muñoz, M.J. Nieto Moreno, N. Giono, L.E. Cambindo Botto, A.E. Dujardin, G. Bastianello, G. Lavore, S. Torres-Méndez, A. Menck, C.F.M. Blencowe, B.J. Irimia, M. Foiani, M. Kornblihtt, A.R. alternative splicing ATR cyclobutane pyrimidine dimers DNA damage global genome repair nucleotide excision repair Potorous photolyase UV irradiation ATR protein cyclobutane deoxyribodipyrimidine photolyase pyrimidine dimer RNA polymerase II ATM protein ATR protein, human DNA pyrimidine dimer RNA polymerase II alternative RNA splicing Article controlled study DNA damage DNA repair DNA synthesis enzyme phosphorylation excision repair gene expression human human cell inhibition kinetics keratinocyte signal transduction transcription initiation ultraviolet irradiation alternative RNA splicing cytology DNA repair genetic transcription genetics metabolism phosphorylation radiation response skin ultraviolet radiation Alternative Splicing Ataxia Telangiectasia Mutated Proteins DNA DNA Repair Humans Keratinocytes Phosphorylation Pyrimidine Dimers RNA Polymerase II Skin Transcription, Genetic Ultraviolet Rays We have previously found that UV irradiation promotes RNA polymerase II (RNAPII) hyperphosphorylation and subsequent changes in alternative splicing (AS). We show now that UV-induced DNA damage is not only necessary but sufficient to trigger the AS response and that photolyase-mediated removal of the most abundant class of pyrimidine dimers (PDs) abrogates the global response to UV. We demonstrate that, in keratinocytes, RNAPII is the target, but not a sensor, of the signaling cascade initiated by PDs. The UV effect is enhanced by inhibition of gap-filling DNA synthesis, the last step in the nucleotide excision repair pathway (NER), and reduced by the absence of XPE, the main NER sensor of PDs. The mechanism involves activation of the protein kinase ATR that mediates the UV-induced RNAPII hyperphosphorylation. Our results define the sequence UV-PDs-NER-ATR-RNAPII-AS as a pathway linking DNA damage repair to the control of both RNAPII phosphorylation and AS regulation. © 2017 The Author(s) Fil:Muñoz, M.J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Giono, L.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Kornblihtt, A.R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_22111247_v18_n12_p2868_Munoz |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
alternative splicing ATR cyclobutane pyrimidine dimers DNA damage global genome repair nucleotide excision repair Potorous photolyase UV irradiation ATR protein cyclobutane deoxyribodipyrimidine photolyase pyrimidine dimer RNA polymerase II ATM protein ATR protein, human DNA pyrimidine dimer RNA polymerase II alternative RNA splicing Article controlled study DNA damage DNA repair DNA synthesis enzyme phosphorylation excision repair gene expression human human cell inhibition kinetics keratinocyte signal transduction transcription initiation ultraviolet irradiation alternative RNA splicing cytology DNA repair genetic transcription genetics metabolism phosphorylation radiation response skin ultraviolet radiation Alternative Splicing Ataxia Telangiectasia Mutated Proteins DNA DNA Repair Humans Keratinocytes Phosphorylation Pyrimidine Dimers RNA Polymerase II Skin Transcription, Genetic Ultraviolet Rays |
| spellingShingle |
alternative splicing ATR cyclobutane pyrimidine dimers DNA damage global genome repair nucleotide excision repair Potorous photolyase UV irradiation ATR protein cyclobutane deoxyribodipyrimidine photolyase pyrimidine dimer RNA polymerase II ATM protein ATR protein, human DNA pyrimidine dimer RNA polymerase II alternative RNA splicing Article controlled study DNA damage DNA repair DNA synthesis enzyme phosphorylation excision repair gene expression human human cell inhibition kinetics keratinocyte signal transduction transcription initiation ultraviolet irradiation alternative RNA splicing cytology DNA repair genetic transcription genetics metabolism phosphorylation radiation response skin ultraviolet radiation Alternative Splicing Ataxia Telangiectasia Mutated Proteins DNA DNA Repair Humans Keratinocytes Phosphorylation Pyrimidine Dimers RNA Polymerase II Skin Transcription, Genetic Ultraviolet Rays Muñoz, M.J. Nieto Moreno, N. Giono, L.E. Cambindo Botto, A.E. Dujardin, G. Bastianello, G. Lavore, S. Torres-Méndez, A. Menck, C.F.M. Blencowe, B.J. Irimia, M. Foiani, M. Kornblihtt, A.R. Major Roles for Pyrimidine Dimers, Nucleotide Excision Repair, and ATR in the Alternative Splicing Response to UV Irradiation |
| topic_facet |
alternative splicing ATR cyclobutane pyrimidine dimers DNA damage global genome repair nucleotide excision repair Potorous photolyase UV irradiation ATR protein cyclobutane deoxyribodipyrimidine photolyase pyrimidine dimer RNA polymerase II ATM protein ATR protein, human DNA pyrimidine dimer RNA polymerase II alternative RNA splicing Article controlled study DNA damage DNA repair DNA synthesis enzyme phosphorylation excision repair gene expression human human cell inhibition kinetics keratinocyte signal transduction transcription initiation ultraviolet irradiation alternative RNA splicing cytology DNA repair genetic transcription genetics metabolism phosphorylation radiation response skin ultraviolet radiation Alternative Splicing Ataxia Telangiectasia Mutated Proteins DNA DNA Repair Humans Keratinocytes Phosphorylation Pyrimidine Dimers RNA Polymerase II Skin Transcription, Genetic Ultraviolet Rays |
| description |
We have previously found that UV irradiation promotes RNA polymerase II (RNAPII) hyperphosphorylation and subsequent changes in alternative splicing (AS). We show now that UV-induced DNA damage is not only necessary but sufficient to trigger the AS response and that photolyase-mediated removal of the most abundant class of pyrimidine dimers (PDs) abrogates the global response to UV. We demonstrate that, in keratinocytes, RNAPII is the target, but not a sensor, of the signaling cascade initiated by PDs. The UV effect is enhanced by inhibition of gap-filling DNA synthesis, the last step in the nucleotide excision repair pathway (NER), and reduced by the absence of XPE, the main NER sensor of PDs. The mechanism involves activation of the protein kinase ATR that mediates the UV-induced RNAPII hyperphosphorylation. Our results define the sequence UV-PDs-NER-ATR-RNAPII-AS as a pathway linking DNA damage repair to the control of both RNAPII phosphorylation and AS regulation. © 2017 The Author(s) |
| format |
JOUR |
| author |
Muñoz, M.J. Nieto Moreno, N. Giono, L.E. Cambindo Botto, A.E. Dujardin, G. Bastianello, G. Lavore, S. Torres-Méndez, A. Menck, C.F.M. Blencowe, B.J. Irimia, M. Foiani, M. Kornblihtt, A.R. |
| author_facet |
Muñoz, M.J. Nieto Moreno, N. Giono, L.E. Cambindo Botto, A.E. Dujardin, G. Bastianello, G. Lavore, S. Torres-Méndez, A. Menck, C.F.M. Blencowe, B.J. Irimia, M. Foiani, M. Kornblihtt, A.R. |
| author_sort |
Muñoz, M.J. |
| title |
Major Roles for Pyrimidine Dimers, Nucleotide Excision Repair, and ATR in the Alternative Splicing Response to UV Irradiation |
| title_short |
Major Roles for Pyrimidine Dimers, Nucleotide Excision Repair, and ATR in the Alternative Splicing Response to UV Irradiation |
| title_full |
Major Roles for Pyrimidine Dimers, Nucleotide Excision Repair, and ATR in the Alternative Splicing Response to UV Irradiation |
| title_fullStr |
Major Roles for Pyrimidine Dimers, Nucleotide Excision Repair, and ATR in the Alternative Splicing Response to UV Irradiation |
| title_full_unstemmed |
Major Roles for Pyrimidine Dimers, Nucleotide Excision Repair, and ATR in the Alternative Splicing Response to UV Irradiation |
| title_sort |
major roles for pyrimidine dimers, nucleotide excision repair, and atr in the alternative splicing response to uv irradiation |
| url |
http://hdl.handle.net/20.500.12110/paper_22111247_v18_n12_p2868_Munoz |
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