Proteomics

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INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double- strand breaks

ABSTRACT: This study shows that Integrator complex subunit 6 (INTS6) associates with the trimeric SOSS1 (comprising INTS3, INIP, and hSSB1) to form a tetrameric SOSS1 complex following DNA damage. INTS6 binds to DNA:RNA hybrids and plays a crucial role in Protein Phosphatase 2 (PP2A) recruitment to DNA double-strand breaks (DSBs), facilitating the dephosphorylation of RNAPII. Furthermore, INTS6 prevents the accumulation of damage-induced RNA transcripts and stabilizes 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. These data demonstrate the significance of the SOSS1 complex in autoregulating DNA:RNA dynamics and the promotion of efficient DNA repair.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Felipe Cesar Ferrarezi Beckedorff  

LAB HEAD: Ramin Shiekhattar

PROVIDER: PXD048694 | Pride | 2025-05-06

REPOSITORIES: Pride

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Publications

Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks.

Long Qilin Q   Ajit Kamal K   Sedova Katerina K   Haluza Vojtech V   Stefl Richard R   Dokaneheifard Sadat S   Beckedorff Felipe F   Valencia Monica G MG   Sebesta Marek M   Shiekhattar Ramin R   Gullerova Monika M  

Nucleic acids research 20241101 21

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 tetram  ...[more]

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