INTS3 (integrator complex subunit 3) functions as a critical scaffold component of the SOSS (sensor of single-stranded DNA) complex, playing dual roles in DNA damage response and transcriptional regulation. In DNA repair, INTS3 stabilizes the heterotrimeric SOSS1 complex with hSSB1 and C9ORF80, facilitating homologous recombination-dependent repair of double-strand breaks and ATM-dependent checkpoint signaling 1. INTS3's N-terminal domain scaffolds complex assembly, while its C-terminal HEAT-repeat domain binds single-stranded nucleic acids and interacts with INTS6 to maintain protein stability 2. The tetrameric INTS6-SOSS1 complex containing INTS3 recruits phosphatase PP2A to dephosphorylate RNA polymerase II and resolve DNA:RNA hybrids at break sites, facilitating efficient repair 3. In transcriptional control, INTS3 participates in Integrator-mediated RNA polymerase II termination, where it prevents Pol II rebinding after transcript cleavage 4. Disease relevance is evidenced in acute myeloid leukemia, where aberrant INTS3 splicing driven by coordinated IDH2 and SRSF2 mutations promotes leukaemogenesis through RNA polymerase II stalling 5. INTS3 represents a potential therapeutic target in cancers with elevated DNA repair activity, as disrupting its interaction with hSSB1 can impair SOSS1 complex function 6.