PMID- 32788234
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20220815
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Linking)
VI  - 133
IP  - 17
DP  - 2020 Sep 4
TI  - The role of the alpha-tubulin acetyltransferase alphaTAT1 in the DNA damage response.
LID - jcs246702 [pii]
LID - 10.1242/jcs.246702 [doi]
AB  - Lysine 40 acetylation of alpha-tubulin (Ac-alpha-tubulin), catalyzed by the 
      acetyltransferase alphaTAT1, marks stabilized microtubules. Recently, there is 
      growing evidence to suggest crosstalk between the DNA damage response (DDR) and 
      microtubule organization; we therefore investigated whether alphaTAT1 is involved in 
      the DDR. Following treatment with DNA-damaging agents, increased levels of 
      Ac-alpha-tubulin were detected. We also observed significant induction of 
      Ac-alpha-tubulin after depletion of DNA repair proteins, suggesting that alphaTAT1 is 
      positively regulated in response to DNA damage. Intriguingly, alphaTAT1 depletion 
      decreased DNA damage-induced replication protein A (RPA) phosphorylation and foci 
      formation. Moreover, DNA damage-induced cell cycle arrest was significantly 
      delayed in alphaTAT1-depleted cells, indicating defective checkpoint activation. The 
      checkpoint defects seen upon alphaTAT1 deficiency were restored by expression of 
      wild-type alphaTAT1, but not by alphaTAT1-D157N (a catalytically inactive alphaTAT1), 
      indicating that the role of alphaTAT1 in the DDR is dependent on enzymatic activity. 
      Furthermore, alphaTAT1-depleted direct repeat GFP (DR-GFP) U2OS cells had a 
      significant decrease in the frequency of homologous recombination repair. 
      Collectively, our results suggest that alphaTAT1 may play an essential role in DNA 
      damage checkpoints and DNA repair through its acetyltransferase activity.
CI  - (c) 2020. Published by The Company of Biologists Ltd.
FAU - Ryu, Na Mi
AU  - Ryu NM
AUID- ORCID: 0000-0002-4610-8573
AD  - Department of Pharmacology, Chonnam National University Medical School, 
      Jellanamdo, 58128, Republic of Korea.
FAU - Kim, Jung Min
AU  - Kim JM
AUID- ORCID: 0000-0002-2004-8533
AD  - Department of Pharmacology, Chonnam National University Medical School, 
      Jellanamdo, 58128, Republic of Korea Jungminkim@jnu.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200904
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Tubulin)
RN  - EC 2.3.1.- (Acetyltransferases)
RN  - EC 2.3.1.108 (alpha-tubulin acetylase)
SB  - IM
MH  - Acetylation
MH  - *Acetyltransferases/genetics/metabolism
MH  - DNA Damage/genetics
MH  - Microtubules/metabolism
MH  - *Tubulin/genetics/metabolism
OTO - NOTNLM
OT  - Checkpoint activation
OT  - DNA damage response
OT  - Homologous recombination repair
OT  - Microtubule stability
OT  - alpha-tubulin acetyltransferase
OT  - alpha-tubulin lysine acetylation
OT  - alphaTAT1
COIS- Competing interestsThe authors declare no competing or financial interests.
EDAT- 2020/08/14 06:00
MHDA- 2021/06/22 06:00
CRDT- 2020/08/14 06:00
PHST- 2020/03/25 00:00 [received]
PHST- 2020/07/27 00:00 [accepted]
PHST- 2020/08/14 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/08/14 06:00 [entrez]
AID - jcs.246702 [pii]
AID - 10.1242/jcs.246702 [doi]
PST - epublish
SO  - J Cell Sci. 2020 Sep 4;133(17):jcs246702. doi: 10.1242/jcs.246702.