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Updated: Sep 14, 2026

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Published on: November 5, 2012
TRRAP enables MMB-dependent mitotic transcription and determines sensitivity to CHK1 inhibition
Franziska Liss1, Dörthe Gertzmann1, Devi Bala Murugan1
1Department of Biochemistry and Cell Biology, Theodor Boveri Institute, Biocenter, Julius Maximilian University Würzburg, Am Hubland, 97074 Würzburg, Germany.
Abstract:
Precise temporal activation of mitotic genes is essential for proper cell-cycle progression, yet the chromatin-based mechanisms coordinating this process remain incompletely understood. The B-MYB-MuvB (MMB) complex is a key regulator of mitotic gene expression and becomes hyperactivated following inhibition of the ATR-CHK1 pathway, resulting in MMB-dependent premature mitotic entry, replication catastrophe, and cell death. Here, we combine proximity-dependent proteomics with a targeted siRNA screen of chromatin regulators using CHK1 inhibitor-induced premature mitosis and DNA damage as functional readouts. We identify TRRAP as a critical regulator of MMB-dependent mitotic transcription. TRRAP physically associates with B-MYB, occupies MMB target promoters, and is required for expression of mitotic genes during both normal G2/M progression and CHK1 inhibitor-induced premature mitosis. Although activation of YAP signaling bypasses the G1 requirement for TRRAP, TRRAP remains essential for G2/M gene expression and mitotic progression. Together, these findings link TRRAP-dependent chromatin regulation to MMB activity and checkpoint sensitivity.
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