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SET7-mediated TIP60 methylation is essential for DNA double-strand break repair.

ABSTRACT: 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. [BMB Reports 2022; 55(11): 541-546].

SUBMITTER: Kim SH

PROVIDER: S-EPMC9712704 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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SET7-mediated TIP60 methylation is essential for DNA double-strand break repair.

Kim Song Hyun SH Park Junyoung J Park Jin Woo JW Hahm Ja Young JY Yoon Seobin S Hwang In Jun IJ Kim Keun Pil KP Seo Sang-Beom SB

BMB reports 20221101 11

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 ...[more]

PMID: 35880433

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