INTS3 controls the hSSB1-mediated DNA damage response

The Journal of Cell Biology
Jeffrey R SkaarMichele Pagano

Abstract

Human SSB1 (single-stranded binding protein 1 [hSSB1]) was recently identified as a part of the ataxia telangiectasia mutated (ATM) signaling pathway. To investigate hSSB1 function, we performed tandem affinity purifications of hSSB1 mutants mimicking the unphosphorylated and ATM-phosphorylated states. Both hSSB1 mutants copurified a subset of Integrator complex subunits and the uncharacterized protein LOC58493/c9orf80 (henceforth minute INTS3/hSSB-associated element [MISE]). The INTS3-MISE-hSSB1 complex plays a key role in ATM activation and RAD51 recruitment to DNA damage foci during the response to genotoxic stresses. These effects on the DNA damage response are caused by the control of hSSB1 transcription via INTS3, demonstrating a new network controlling hSSB1 function.

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Related Concepts

Transfection
DAPI hydrochloride
INTS3 gene
Response to DNA Damage Stimulus
Signal Transduction Pathways
SSBP1 protein, human
Kidney
Etiology
RAD51 gene
Site of Double-strand Break

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