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SET7-mediated TIP60 methylation is essential for DNA double-strand break repair
Sang Beom Seo 1,* (Professor), Song Hyun Kim1 (Graduate student), Junyoung Park2 (Graduate student), Jin Woo Park3 (Post-doc), Ja Young Hahm4 (Post-doc), Seobin Yoon5 (Graduate student), In Jun Hwang6 (Graduate student), Keun Pil Kim7 (Professor)
1Life Science, Chung-Ang University
The repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) is crucial for maintaining genomic integrity and is involved in numerous fundamental biological processes. Post-translational modifications by proteins play an important role in regulating DNA repair. Here, we report that the methyltransferase SET7 regulates HR-mediated DSB repair by methylating TIP60, a histone acetyltransferase and tumor suppressor involved in gene expression and protein stability. We show that SET7 targets TIP60 for methylation at K137, which facilitates DSB repair by promoting HR and determines cell viability against DNA damage. Interestingly, TIP60 demethylation is catalyzed by LSD1, which affects HR efficiency. Taken together, our findings reveal the importance of TIP60 methylation status by SET7 and LSD1 in the DSB repair pathway.
Abstract, Accepted Manuscript(in press) [Submitted on May 3, 2022, Accepted on July 5, 2022]
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