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Transcription factor moonlights

ATF2, which functions in gene regulation, has another job working in DNA damage response

Graciela Flores(graciela_flores@nasw.org)

Activating transcription factor 2 (ATF2), known for its function in gene regulation, has another totally unrelated role in responding to DNA damage, US researchers report in Molecular Cell this week.

"Here, we show for the first time that a transcription factor has a function in the DNA damage response that is completely independent of its transcriptional activity," Ze'ev Ronai, of the Burnham Institute in La Jolla, Calif., told The Scientist.

For its transcriptional regulatory roles, ATF2 is activated by phosphorylation via the JNK/p38 pathway. The group found alternate phosphorylation sites at serines 490 and 498 that are generally recognized by the kinase ataxia telangiectasia mutated (ATM), which is implicated in double-strand break (DSB) repair. They found ATF2 phosphorylated at those serines localizing at irradiation-induced DSB repair foci. When they inhibited JNK/p38 or disrupted transcriptional regulatory activity of ATF2, the protein continued to show up at these DSBs...

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