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Mol Cell. 2011 Feb 18;41(4):371-83. doi: 10.1016/j.molcel.2011.01.020.

The ATM kinase induces microRNA biogenesis in the DNA damage response.

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Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.


The DNA damage response involves a complex network of processes that detect and repair DNA damage. Here we show that miRNA biogenesis is globally induced upon DNA damage in an ATM-dependent manner. About one-fourth of miRNAs are significantly upregulated after DNA damage, while loss of ATM abolishes their induction. KH-type splicing regulatory protein (KSRP) is a key player that translates DNA damage signaling to miRNA biogenesis. The ATM kinase directly binds to and phosphorylates KSRP, leading to enhanced interaction between KSRP and pri-miRNAs and increased KSRP activity in miRNA processing. Mutations of the ATM phosphorylation sites of KSRP impaired its activity in regulating miRNAs. These findings reveal a mechanism by which DNA damage signaling is linked to miRNA biogenesis.

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