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The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins. It is an adapter protein, which is found in various multiprotein chromatin complexes with histone acetyltransferase activity (HAT), which gives a specific tag for epigenetic transcription activation. TRRAP plays a central role in MYC (c-Myc) transcription activation, and also participates in cell transformation by MYC. It is required for TP53/p53-, E2F1- and E2F4-mediated transcription activation. It most likely acts by linking transcription factors such as E1A, MYC or E2F1 to HAT complexes such as STAGA thereby allowing transcription activation and it is probably not required in the steps following histone acetylation in processes of transcription activation. TRRAP may also be required for the mitotic checkpoint and normal cell cycle progression.