Open AccessThe role of α tubulin acetyltransferase αTAT1 in DNA damage response
Author(s) -
Na Mi Ryu,
Jung Min Kim
Publication year - 2020
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.246702
Subject(s) - dna damage , acetyltransferase , acetylation , biology , tubulin , dna , microtubule , dna repair , microbiology and biotechnology , biochemistry , gene
Lysine 40 acetylation of α tubulin (Ac-α tubulin) catalyzed by acetyltransferase αTAT1, marks stabilized microtubules. Recently, there is growing evidence to suggest the crosstalk between DNA damage response (DDR) and microtubule organization, we therefore investigated whether αTAT1 is involved in DDR. Following treatment with DNA damaging agents, increased levels of Ac-α tubulin were detected. We also observed significant induction of Ac-α tubulin after depletion of DNA repair proteins, suggesting that αTAT1 is positively regulated in response to DNA damage. Intriguingly, αTAT1 depletion decreased DNA damage-induced RPA phosphorylation and foci formation. Moreover, DNA damage -induced cell cycle arrest was significantly delayed in αTAT1-depleted cells, indicating defective checkpoint activation. The checkpoint defects by αTAT1 deficiency were restored by expression of wild-type αTAT1, but not by D157N αTAT1 (catalytically inactive αTAT1), indicating that the role of αTAT1 in the DDR is dependent on enzymatic activity. Furthermore, αTAT1-depleted DR-GFP U2OS cells resulted in a significant decrease in the frequency of homologous recombination repair. Collectively, our results suggest that αTAT1 may play an essential role in DNA damage checkpoints and DNA repair through its acetyltransferase activity.