TRRAP enables MMB-dependent mitotic transcription and determines sensitivity to CHK1 inhibition

The B-MYB-MuvB (MMB) complex is a key regulator of mitotic gene expression and is activated upon inhibition of the ATR-CHK1 pathway, resulting in premature mitotic entry, replication catastrophe, and cell death. Here we identify the transcriptional co-factor TRRAP as a critical regulator of MMB-dependent mitotic transcription. TRRAP physically interacts with B-MYB and is required for the expression of MMB target genes during both normal G2/M progression and CHK1-inhibitor-induced premature mitosis. These results identify TRRAP as a critical chromatin co-factor for MMB-driven mitotic transcription, linking chromatin regulation to checkpoint sensitivity and highlighting a potential vulnerability in cancer cells.