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- Title
INTS3 controls the hSSB1-mediated DNA damage response.
- Authors
Skaar, Jeffrey R.; Richard, Derek J.; Saraf, Anita; Toschi, Alfredo; Bolderson, Emma; Florens, Laurence; Washburn, Michael P.; Khanna, Kum Kum; Pagano, Michele
- 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/hSSBassociated 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.
- Subjects
CARRIER proteins; ATAXIA telangiectasia; GENETIC mutation; DNA damage; GENETIC toxicology; GENETIC transcription
- Publication
Journal of Cell Biology, 2009, Vol 187, Issue 1, p25
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200907026