INTS3 controls the hSSB1-mediated DNA damage response

J Cell Biol. 2009 Oct 5;187(1):25-32. doi: 10.1083/jcb.200907026. Epub 2009 Sep 28.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line
  • Cell Line, Tumor
  • DNA Damage*
  • DNA-Binding Proteins / metabolism*
  • Female
  • Fluorescent Antibody Technique, Direct
  • Fluorescent Dyes / metabolism
  • Humans
  • Indoles / metabolism
  • Kidney / cytology
  • Mitochondrial Proteins
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • RNA, Small Interfering / metabolism
  • Retroviridae / genetics
  • Transfection


  • DNA-Binding Proteins
  • Fluorescent Dyes
  • INTS3 protein, human
  • Indoles
  • Mitochondrial Proteins
  • RNA, Small Interfering
  • SSBP1 protein, human
  • DAPI