KAT5 acetylates ATM at DNA DSBs

Stable Identifier
R-HSA-5682044
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

The histone acetyltransferase Tip60 (KAT5), in addition to forming a histone acetyltransferase complex with NuA4, forms another complex with ATM dimers. The ATM dimer:KAT5 complex is formed in the absence of DNA damage, but the acetyltransferase activity of KAT5 is activated by double strand DNA breaks (DNA DSBs) (Sun et al. 2005). In response to DNA DSBs, the MRN complex targets KAT5 to chromatin, where KAT5 associates with histone H3 trimethylated on lysine 10 (commonly known as H3K9me3 mark). Besides the MRN complex, the ability of KAT5 to access H3K9me3 depends on the DNA damage-induced displacement of HP1beta (CBX1) from H3K9me3 (Ayoub et al. 2008). Binding to H3K9me3 activates the acetyltransferase activity of KAT5 (Sun et al. 2009). KAT5 acetylates ATM on lysine residue K3016 in the highly conserved C-terminal FATC domain of ATM. ATM acetylation is needed for the activation of ATM kinase activity in response to DNA damage (Sun et al. 2007).

Literature References
PubMed ID Title Journal Year
18438399 HP1-beta mobilization promotes chromatin changes that initiate the DNA damage response

Ayoub, N, Jeyasekharan, AD, Bernal, JA, Venkitaraman, AR

Nature 2008
16141325 A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM

Sun, Y, Jiang, X, Chen, S, Fernandes, N, Price, BD

Proc. Natl. Acad. Sci. U.S.A. 2005
19783983 Histone H3 methylation links DNA damage detection to activation of the tumour suppressor Tip60

Sun, Y, Jiang, X, Xu, Y, Ayrapetov, MK, Moreau, LA, Whetstine, JR, Price, BD

Nat. Cell Biol. 2009
17923702 DNA damage-induced acetylation of lysine 3016 of ATM activates ATM kinase activity

Sun, Y, Xu, Y, Roy, K, Price, BD

Mol. Cell. Biol. 2007
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
acetyltransferase activity of DNA DSBs:MRN:ATM dimer:KAT5 [nucleoplasm]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed