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Transcriptional elongation requires DNA break-induced signalling

We have previously shown that RNA polymerase II (Pol II) pause release and transcriptional elongation involve phosphorylation of the factor TRIM28 by the DNA damage response (DDR) kinases ATM and DNA-PK. Here we report a significant role for DNA breaks and DDR signalling in the mechanisms of transcr...

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Autores principales: Bunch, Heeyoun, Lawney, Brian P., Lin, Yu-Fen, Asaithamby, Aroumougame, Murshid, Ayesha, Wang, Yaoyu E., Chen, Benjamin P. C., Calderwood, Stuart K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703865/
https://www.ncbi.nlm.nih.gov/pubmed/26671524
http://dx.doi.org/10.1038/ncomms10191
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author Bunch, Heeyoun
Lawney, Brian P.
Lin, Yu-Fen
Asaithamby, Aroumougame
Murshid, Ayesha
Wang, Yaoyu E.
Chen, Benjamin P. C.
Calderwood, Stuart K.
author_facet Bunch, Heeyoun
Lawney, Brian P.
Lin, Yu-Fen
Asaithamby, Aroumougame
Murshid, Ayesha
Wang, Yaoyu E.
Chen, Benjamin P. C.
Calderwood, Stuart K.
author_sort Bunch, Heeyoun
collection PubMed
description We have previously shown that RNA polymerase II (Pol II) pause release and transcriptional elongation involve phosphorylation of the factor TRIM28 by the DNA damage response (DDR) kinases ATM and DNA-PK. Here we report a significant role for DNA breaks and DDR signalling in the mechanisms of transcriptional elongation in stimulus-inducible genes in humans. Our data show the enrichment of TRIM28 and γH2AX on serum-induced genes and the important function of DNA-PK for Pol II pause release and transcriptional activation-coupled DDR signalling on these genes. γH2AX accumulation decreases when P-TEFb is inhibited, confirming that DDR signalling results from transcriptional elongation. In addition, transcriptional elongation-coupled DDR signalling involves topoisomerase II because inhibiting this enzyme interferes with Pol II pause release and γH2AX accumulation. Our findings propose that DDR signalling is required for effective Pol II pause release and transcriptional elongation through a novel mechanism involving TRIM28, DNA-PK and topoisomerase II.
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spelling pubmed-47038652016-01-22 Transcriptional elongation requires DNA break-induced signalling Bunch, Heeyoun Lawney, Brian P. Lin, Yu-Fen Asaithamby, Aroumougame Murshid, Ayesha Wang, Yaoyu E. Chen, Benjamin P. C. Calderwood, Stuart K. Nat Commun Article We have previously shown that RNA polymerase II (Pol II) pause release and transcriptional elongation involve phosphorylation of the factor TRIM28 by the DNA damage response (DDR) kinases ATM and DNA-PK. Here we report a significant role for DNA breaks and DDR signalling in the mechanisms of transcriptional elongation in stimulus-inducible genes in humans. Our data show the enrichment of TRIM28 and γH2AX on serum-induced genes and the important function of DNA-PK for Pol II pause release and transcriptional activation-coupled DDR signalling on these genes. γH2AX accumulation decreases when P-TEFb is inhibited, confirming that DDR signalling results from transcriptional elongation. In addition, transcriptional elongation-coupled DDR signalling involves topoisomerase II because inhibiting this enzyme interferes with Pol II pause release and γH2AX accumulation. Our findings propose that DDR signalling is required for effective Pol II pause release and transcriptional elongation through a novel mechanism involving TRIM28, DNA-PK and topoisomerase II. Nature Publishing Group 2015-12-16 /pmc/articles/PMC4703865/ /pubmed/26671524 http://dx.doi.org/10.1038/ncomms10191 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Bunch, Heeyoun
Lawney, Brian P.
Lin, Yu-Fen
Asaithamby, Aroumougame
Murshid, Ayesha
Wang, Yaoyu E.
Chen, Benjamin P. C.
Calderwood, Stuart K.
Transcriptional elongation requires DNA break-induced signalling
title Transcriptional elongation requires DNA break-induced signalling
title_full Transcriptional elongation requires DNA break-induced signalling
title_fullStr Transcriptional elongation requires DNA break-induced signalling
title_full_unstemmed Transcriptional elongation requires DNA break-induced signalling
title_short Transcriptional elongation requires DNA break-induced signalling
title_sort transcriptional elongation requires dna break-induced signalling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703865/
https://www.ncbi.nlm.nih.gov/pubmed/26671524
http://dx.doi.org/10.1038/ncomms10191
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