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