The cell response to endogenous DNA damage is still largely unexplored. The paper published on Nucleic Acids Research by Alessandra Montecucco laboratory demonstrates that splicing factor SRSF1 is hyper-phosphorylated in response to increased levels of replication-dependent DNA damage in DNA ligase I defective cells. This is accompanied by a change in alternative splicing events controlled by SRSF1 such as the production of Ron oncogene and caspase 9 alternative mRNAs. Both SRSF1 phosphorylation and splicing programs revert to those found in normal cells by correcting the replication defect or by inhibiting the checkpoint kinase ATM. SRSF1 phosphorylation is also modulated upon treatment with exogenous DNA damaging agents, unveiling a new role of SRSF1 modification in the DNA damage response.
Reference: Leva V, Giuliano S, Bardoni A, Cameini S, Crescenzi M, Lisa A, Biamonti G, Montecucco A. Nucleic Acids Res. 2011,doi:10.1093/nar/gkr837
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