DNA damage induces N-acetyltransferase NAT10 gene expression through transcriptional activation.
NAT10 (N-acetyltransferase 10) is a protein with histone acetylation activity and primarily identified to be involved in regulation of telomerase activity. The presented research shows its transcriptional activation by genotoxic agents and possible role in DNA damage. NAT10 mRNA could be markedly increased by using hydrogen peroxide (H2O2) or cisplatin in a dose- and time-dependent way, and the immunofluorescent staining revealed that the treatment of H2O2 or cisplatin induced focal accumulation of NAT10 protein in cellular nuclei. Both H2O2 and cisplatin could stimulate the transcriptional activity of the NAT10 promoter through the upstream sequences from -615 bp to +110 bp, with which some nuclear proteins interacted. Ectopic expression of NAT10 could enhance the number of survival cells in the presence of H2O2 or cisplatin. The above results suggested that NAT10 could be involved in DNA damage response and increased cellular resistance to genotoxicity.
Liu
Haijing
H
Department of Pathology, Health Science Center of Peking University, 38 Road Xueyuan, Haidian District, Beijing 100083, China.
Ling
Yun
Y
Gong
Yilei
Y
Sun
Ying
Y
Hou
Lin
L
Zhang
Bo
B
D000123:Acetyltransferases / Q000096:biosynthesis* / Q000235:genetics*; D001191:Arylamine N-Acetyltransferase / Q000096:biosynthesis* / Q000235:genetics*; D001483:Base Sequence; D004249:DNA Damage; D004351:Drug Resistance; D004790:Enzyme Induction / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009153:Mutagens / Q000494:pharmacology; D063213:N-Terminal Acetyltransferase E; D063206:N-Terminal Acetyltransferases; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*
D009153:Mutagens; D012333:RNA, Messenger; D000123:Acetyltransferases; D063213:N-Terminal Acetyltransferase E; D001191:Arylamine N-Acetyltransferase; D063206:N-Terminal Acetyltransferases; C522989:NAT10 protein, human