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Functional transcription promoters at DNA double-strand breaks mediate RNA-driven phase separation of damage response factors
Damage-induced long non-coding RNAs (dilncRNA) synthesized at DNA double-strand breaks (DSBs) by RNA polymerase II (RNAPII) are necessary for DNA damage response (DDR) foci formation. We demonstrate that induction of DSBs results in the assembly of functional promoters that include a complete RNAPII...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859070/ https://www.ncbi.nlm.nih.gov/pubmed/31570834 http://dx.doi.org/10.1038/s41556-019-0392-4 |
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author | Pessina, Fabio Giavazzi, Fabio Yin, Yandong Gioia, Ubaldo Vitelli, Valerio Galbiati, Alessandro Barozzi, Sara Garre, Massimiliano Oldani, Amanda Flaus, Andrew Cerbino, Roberto Parazzoli, Dario Rothenberg, Eli di Fagagna, Fabrizio d’Adda |
author_facet | Pessina, Fabio Giavazzi, Fabio Yin, Yandong Gioia, Ubaldo Vitelli, Valerio Galbiati, Alessandro Barozzi, Sara Garre, Massimiliano Oldani, Amanda Flaus, Andrew Cerbino, Roberto Parazzoli, Dario Rothenberg, Eli di Fagagna, Fabrizio d’Adda |
author_sort | Pessina, Fabio |
collection | PubMed |
description | Damage-induced long non-coding RNAs (dilncRNA) synthesized at DNA double-strand breaks (DSBs) by RNA polymerase II (RNAPII) are necessary for DNA damage response (DDR) foci formation. We demonstrate that induction of DSBs results in the assembly of functional promoters that include a complete RNAPII pre-initiation complex (PIC), MED1 and CDK9. Absence or inactivation of these factors causes DDR foci reduction both in vivo and in an in vitro system that reconstitutes DDR events on nucleosomes. We also show that dilncRNAs drive molecular crowding of DDR proteins such as 53BP1 into foci that exhibit liquid-liquid phase separation (LLPS) condensate properties. We propose that the assembly of DSB-induced transcriptional promoters drives RNA synthesis which stimulates phase separation of DDR factors in the shape of foci. |
format | Online Article Text |
id | pubmed-6859070 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-68590702020-03-30 Functional transcription promoters at DNA double-strand breaks mediate RNA-driven phase separation of damage response factors Pessina, Fabio Giavazzi, Fabio Yin, Yandong Gioia, Ubaldo Vitelli, Valerio Galbiati, Alessandro Barozzi, Sara Garre, Massimiliano Oldani, Amanda Flaus, Andrew Cerbino, Roberto Parazzoli, Dario Rothenberg, Eli di Fagagna, Fabrizio d’Adda Nat Cell Biol Article Damage-induced long non-coding RNAs (dilncRNA) synthesized at DNA double-strand breaks (DSBs) by RNA polymerase II (RNAPII) are necessary for DNA damage response (DDR) foci formation. We demonstrate that induction of DSBs results in the assembly of functional promoters that include a complete RNAPII pre-initiation complex (PIC), MED1 and CDK9. Absence or inactivation of these factors causes DDR foci reduction both in vivo and in an in vitro system that reconstitutes DDR events on nucleosomes. We also show that dilncRNAs drive molecular crowding of DDR proteins such as 53BP1 into foci that exhibit liquid-liquid phase separation (LLPS) condensate properties. We propose that the assembly of DSB-induced transcriptional promoters drives RNA synthesis which stimulates phase separation of DDR factors in the shape of foci. 2019-09-30 2019-10 /pmc/articles/PMC6859070/ /pubmed/31570834 http://dx.doi.org/10.1038/s41556-019-0392-4 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Pessina, Fabio Giavazzi, Fabio Yin, Yandong Gioia, Ubaldo Vitelli, Valerio Galbiati, Alessandro Barozzi, Sara Garre, Massimiliano Oldani, Amanda Flaus, Andrew Cerbino, Roberto Parazzoli, Dario Rothenberg, Eli di Fagagna, Fabrizio d’Adda Functional transcription promoters at DNA double-strand breaks mediate RNA-driven phase separation of damage response factors |
title | Functional transcription promoters at DNA double-strand breaks mediate RNA-driven phase separation of damage response factors |
title_full | Functional transcription promoters at DNA double-strand breaks mediate RNA-driven phase separation of damage response factors |
title_fullStr | Functional transcription promoters at DNA double-strand breaks mediate RNA-driven phase separation of damage response factors |
title_full_unstemmed | Functional transcription promoters at DNA double-strand breaks mediate RNA-driven phase separation of damage response factors |
title_short | Functional transcription promoters at DNA double-strand breaks mediate RNA-driven phase separation of damage response factors |
title_sort | functional transcription promoters at dna double-strand breaks mediate rna-driven phase separation of damage response factors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859070/ https://www.ncbi.nlm.nih.gov/pubmed/31570834 http://dx.doi.org/10.1038/s41556-019-0392-4 |
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