Journal
CELL CYCLE
Volume 8, Issue 22, Pages 3717-3722Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.8.22.10025
Keywords
DNA-PK; DNA double-strand breaks; DNA repair; SAF-A; phosphorylation; NHEJ
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Funding
- CNRS
- Ligue Nationale Contre le Cancer (equipe labellisee)
- Commissariat a l'Energie Atomique (CEA)
- Fondation pour la Recherche Medicale (FRM)
- Canceropole Grand Sud Ouest and the Institut National du Cancer (INCa)
- Fondation pour la Recherche Medicale [FDT20080913845]
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Aiming to identify novel phosphorylation sites in response to DNA double-strand breaks (DSB) inducers, we have isolated a phosphorylation site on KU70. Unexpectedly, a rabbit antiserum raised against this site cross-reacted with a 120 kDa protein in cells treated by DNA DSB inducers. We identified this protein as SAF-A/hnRNP U, an abundant and essential nuclear protein containing regions binding DNA or RNA. The phosphorylation site was mapped at S59 position in a sequence context favoring a S-hydrophobic consensus model for DNA-PK phosphorylation site in vivo. This site was exclusively phosphorylated by DNA-PK in response to DNA DSB inducers. In addition, the extent and duration of this phosphorylation was in inverse correlation with the capacity of the cells to repair DSB by Nonhomologous End Joining. These results bring a new link between the hnRNP family and the DNA damage response. Addtionaly, the mapped phospho-site on SAF-A might serve as a potential bio-marker for DNA-PK activity in academic studies and clinical analyses of DNA-PK activators or inhibitors.
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