Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks
DNA double-strand breaks (DSBs) represent a lethal form of DNA damage that can trigger cell death or initiate oncogenesis. The activity of RNA polymerase II (RNAPII) at the break site is required for efficient DSB repair. However, the regulatory mechanisms governing the transcription cycle at DSBs a...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2024
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| _version_ | 1817931710491262976 |
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| author | Long, Q Ajit, K Sedova, K Haluza, V Stefl, R Dokaneheifard, S Beckedorff, F Valencia, M Sebesta, M Shiekhattar, R Gullerova, M |
| author_facet | Long, Q Ajit, K Sedova, K Haluza, V Stefl, R Dokaneheifard, S Beckedorff, F Valencia, M Sebesta, M Shiekhattar, R Gullerova, M |
| author_sort | Long, Q |
| collection | OXFORD |
| description | DNA double-strand breaks (DSBs) represent a lethal form of DNA damage that can trigger cell death or initiate oncogenesis. The activity of RNA polymerase II (RNAPII) at the break site is required for efficient DSB repair. However, the regulatory mechanisms governing the transcription cycle at DSBs are not well understood. Here, we show that Integrator complex subunit 6 (INTS6) associates with the heterotrimeric sensor of ssDNA (SOSS1) complex (comprising INTS3, INIP and hSSB1) to form the tetrameric SOSS1 complex. INTS6 binds to DNA:RNA hybrids and promotes Protein Phosphatase 2A (PP2A) recruitment to DSBs, facilitating the dephosphorylation of RNAPII. Furthermore, INTS6 prevents the accumulation of damage-associated RNA transcripts (DARTs) and the stabilization of DNA:RNA hybrids at DSB sites. INTS6 interacts with and promotes the recruitment of senataxin (SETX) to DSBs, facilitating the resolution of DNA:RNA hybrids/R-loops. Our results underscore the significance of the tetrameric SOSS1 complex in the autoregulation of DNA:RNA hybrids and efficient DNA repair. |
| first_indexed | 2024-12-09T03:26:21Z |
| format | Journal article |
| id | oxford-uuid:6ce308b0-ba12-4395-89ae-a318ef384cb7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:26:21Z |
| publishDate | 2024 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:6ce308b0-ba12-4395-89ae-a318ef384cb72024-11-28T20:10:18ZTetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaksJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6ce308b0-ba12-4395-89ae-a318ef384cb7EnglishJisc Publications RouterOxford University Press2024Long, QAjit, KSedova, KHaluza, VStefl, RDokaneheifard, SBeckedorff, FValencia, MSebesta, MShiekhattar, RGullerova, MDNA double-strand breaks (DSBs) represent a lethal form of DNA damage that can trigger cell death or initiate oncogenesis. The activity of RNA polymerase II (RNAPII) at the break site is required for efficient DSB repair. However, the regulatory mechanisms governing the transcription cycle at DSBs are not well understood. Here, we show that Integrator complex subunit 6 (INTS6) associates with the heterotrimeric sensor of ssDNA (SOSS1) complex (comprising INTS3, INIP and hSSB1) to form the tetrameric SOSS1 complex. INTS6 binds to DNA:RNA hybrids and promotes Protein Phosphatase 2A (PP2A) recruitment to DSBs, facilitating the dephosphorylation of RNAPII. Furthermore, INTS6 prevents the accumulation of damage-associated RNA transcripts (DARTs) and the stabilization of DNA:RNA hybrids at DSB sites. INTS6 interacts with and promotes the recruitment of senataxin (SETX) to DSBs, facilitating the resolution of DNA:RNA hybrids/R-loops. Our results underscore the significance of the tetrameric SOSS1 complex in the autoregulation of DNA:RNA hybrids and efficient DNA repair. |
| spellingShingle | Long, Q Ajit, K Sedova, K Haluza, V Stefl, R Dokaneheifard, S Beckedorff, F Valencia, M Sebesta, M Shiekhattar, R Gullerova, M Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks |
| title | Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks |
| title_full | Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks |
| title_fullStr | Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks |
| title_full_unstemmed | Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks |
| title_short | Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks |
| title_sort | tetrameric ints6 soss1 complex facilitates dna rna hybrid autoregulation at double strand breaks |
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