TIP60

Histone acetyltransferase TIP60 (KAT5) is a member of the MYST family of lysine acetyltransferases and functions as the catalytic core of the evolutionarily conserved NuA4 chromatin-modifying complex, where it promotes histone acetylation and transcriptional regulation^[1][2]. Mechanistically, TIP60 plays a central role in the DNA damage response by interacting with and acetylating key DNA repair regulators, including ataxia-telangiectasia mutated (ATM), thereby facilitating ATM activation following DNA double-strand breaks^[1][3][4]. Following DNA damage, the NuA4/TIP60 complex is recruited to chromatin surrounding DNA lesions and contributes to chromatin remodeling events that support efficient DNA repair^[1][5]. TIP60 also regulates the acetylation of multiple non-histone proteins involved in genome maintenance, highlighting its broad role in preserving cell viability and genomic stability^[2]. In disease contexts, reduced TIP60 activity or expression has been associated with genomic instability, and experimental evidence supports a tumor-suppressive role for TIP60 in breast cancer models^[6]. Beyond cancer, genetic studies demonstrate that TIP60 is required for neural stem cell maintenance, neurogenesis, and normal brain development, indicating functions that extend beyond canonical DNA repair pathways^[7]. Compared with related MYST acetyltransferases, TIP60 is distinguished by its direct coupling of chromatin sensing and ATM-dependent DNA damage signaling, making it a widely used experimental model for investigating chromatin-regulated genome surveillance mechanisms^[1][3][4].