Tip60

Tip60, also known as KAT5 (lysine acetyltransferase 5), is a member of the MYST family of histone acetyltransferases. In humans it functions as the catalytic subunit of the TIP60 complex, a multi-subunit chromatin-remodeling and histone-modifying complex that shares homology with the yeast NuA4 complex.

Function: The Tip60 enzyme acetylates lysine residues on histone tails, most notably histones H4 and H2A variants, leading to relaxed chromatin and modulation of transcription. It also acetylates non-histone substrates such as p53 and components of the DNA damage response pathway, affecting cell cycle control and apoptosis.

DNA damage response: TIP60 activity is recruited to sites of DNA double-strand breaks and contributes to chromatin relaxation that facilitates repair. It activates the ATM kinase by acetylating it, promoting downstream signaling required for homologous recombination and non-homologous end joining. TIP60-mediated acetylation of histones near break sites also helps recruitment of repair factors such as BRCA1 and 53BP1.

Transcription regulation: Through its histone acetyltransferase activity and interactions with transcription factors and coactivators, TIP60 influences the transcriptional program in development, stress responses, and metabolism.

Clinical and developmental relevance: Tip60 is essential for embryonic development in mice, and altered expression or activity has been reported in various human cancers, where it can act as a tumor suppressor in some contexts or participate in tumor progression in others. The TIP60 complex also participates in other chromatin-related processes, including chromatin remodeling and response to stress.