Damage-induced long non-coding RNAs (dilncRNA) synthesized at DNA double-strand breaks (DSBs) by RNA polymerase II are necessary for DNA-damage-response (DDR) focus formation. We demonstrate that induction of DSBs results in the assembly of functional promoters that include a complete RNA polymerase II preinitiation complex, MED1 and CDK9. Absence or inactivation of these factors causes a reduction in DDR foci 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 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.

Functional transcription promoters at DNA double-strand breaks mediate RNA-driven phase separation of damage-response factors / F. Pessina, F. Giavazzi, Y. Yin, U. Gioia, V. Vitelli, A. Galbiati, S. Barozzi, M. Garre, A. Oldani, A. Flaus, R. Cerbino, D. Parazzoli, E. Rothenberg, F. d'Adda di Fagagna. - In: NATURE CELL BIOLOGY. - ISSN 1465-7392. - 21:10(2019 Oct), pp. 1286-1299. [10.1038/s41556-019-0392-4]

Functional transcription promoters at DNA double-strand breaks mediate RNA-driven phase separation of damage-response factors

Giavazzi F.;Cerbino R.;
2019-10

Abstract

Damage-induced long non-coding RNAs (dilncRNA) synthesized at DNA double-strand breaks (DSBs) by RNA polymerase II are necessary for DNA-damage-response (DDR) focus formation. We demonstrate that induction of DSBs results in the assembly of functional promoters that include a complete RNA polymerase II preinitiation complex, MED1 and CDK9. Absence or inactivation of these factors causes a reduction in DDR foci 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 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.
Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin)
Settore FIS/03 - Fisica della Materia
Light for Life
30-set-2019
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/689026
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