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Phosphorylation of SRSF1 is modulated by replicational stress
DNA ligase I-deficient 46BR.1G1 cells show a delay in the maturation of replicative intermediates resulting in the accumulation of single- and double-stranded DNA breaks. As a consequence the ataxia telangiectasia mutated protein kinase (ATM) is constitutively phosphorylated at a basal level. Here,...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273819/ https://www.ncbi.nlm.nih.gov/pubmed/21984412 http://dx.doi.org/10.1093/nar/gkr837 |
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author | Leva, Valentina Giuliano, Serena Bardoni, Anna Camerini, Serena Crescenzi, Marco Lisa, Antonella Biamonti, Giuseppe Montecucco, Alessandra |
author_facet | Leva, Valentina Giuliano, Serena Bardoni, Anna Camerini, Serena Crescenzi, Marco Lisa, Antonella Biamonti, Giuseppe Montecucco, Alessandra |
author_sort | Leva, Valentina |
collection | PubMed |
description | DNA ligase I-deficient 46BR.1G1 cells show a delay in the maturation of replicative intermediates resulting in the accumulation of single- and double-stranded DNA breaks. As a consequence the ataxia telangiectasia mutated protein kinase (ATM) is constitutively phosphorylated at a basal level. Here, we use 46BR.1G1 cells as a model system to study the cell response to chronic replication-dependent DNA damage. Starting from a proteomic approach, we demonstrate that the phosphorylation level of factors controlling constitutive and alternative splicing is affected by the damage elicited by DNA ligase I deficiency. In particular, we show that SRSF1 is hyperphosphorylated in 46BR.1G1 cells compared to control fibroblasts. This hyperphosphorylation can be partially prevented by inhibiting ATM activity with caffeine. Notably, hyperphosphorylation of SRSF1 affects the subnuclear distribution of the protein and the alternative splicing pattern of target genes. We also unveil a modulation of SRSF1 phosphorylation after exposure of MRC-5V1 control fibroblasts to different exogenous sources of DNA damage. Altogether, our observations indicate that a relevant aspect of the cell response to DNA damage involves the post-translational regulation of splicing factor SRSF1 which is associated with a shift in the alternative splicing program of target genes to control cell survival or cell death. |
format | Online Article Text |
id | pubmed-3273819 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-32738192012-02-07 Phosphorylation of SRSF1 is modulated by replicational stress Leva, Valentina Giuliano, Serena Bardoni, Anna Camerini, Serena Crescenzi, Marco Lisa, Antonella Biamonti, Giuseppe Montecucco, Alessandra Nucleic Acids Res Genome Integrity, Repair and Replication DNA ligase I-deficient 46BR.1G1 cells show a delay in the maturation of replicative intermediates resulting in the accumulation of single- and double-stranded DNA breaks. As a consequence the ataxia telangiectasia mutated protein kinase (ATM) is constitutively phosphorylated at a basal level. Here, we use 46BR.1G1 cells as a model system to study the cell response to chronic replication-dependent DNA damage. Starting from a proteomic approach, we demonstrate that the phosphorylation level of factors controlling constitutive and alternative splicing is affected by the damage elicited by DNA ligase I deficiency. In particular, we show that SRSF1 is hyperphosphorylated in 46BR.1G1 cells compared to control fibroblasts. This hyperphosphorylation can be partially prevented by inhibiting ATM activity with caffeine. Notably, hyperphosphorylation of SRSF1 affects the subnuclear distribution of the protein and the alternative splicing pattern of target genes. We also unveil a modulation of SRSF1 phosphorylation after exposure of MRC-5V1 control fibroblasts to different exogenous sources of DNA damage. Altogether, our observations indicate that a relevant aspect of the cell response to DNA damage involves the post-translational regulation of splicing factor SRSF1 which is associated with a shift in the alternative splicing program of target genes to control cell survival or cell death. Oxford University Press 2012-02 2011-10-07 /pmc/articles/PMC3273819/ /pubmed/21984412 http://dx.doi.org/10.1093/nar/gkr837 Text en © The Author(s) 2011. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Genome Integrity, Repair and Replication Leva, Valentina Giuliano, Serena Bardoni, Anna Camerini, Serena Crescenzi, Marco Lisa, Antonella Biamonti, Giuseppe Montecucco, Alessandra Phosphorylation of SRSF1 is modulated by replicational stress |
title | Phosphorylation of SRSF1 is modulated by replicational stress |
title_full | Phosphorylation of SRSF1 is modulated by replicational stress |
title_fullStr | Phosphorylation of SRSF1 is modulated by replicational stress |
title_full_unstemmed | Phosphorylation of SRSF1 is modulated by replicational stress |
title_short | Phosphorylation of SRSF1 is modulated by replicational stress |
title_sort | phosphorylation of srsf1 is modulated by replicational stress |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273819/ https://www.ncbi.nlm.nih.gov/pubmed/21984412 http://dx.doi.org/10.1093/nar/gkr837 |
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