Author:
Du Juan,Liu Yang,Lu Lu,Shi Jianfei,Xu Longqian,Li Qi,Cheng Xiaofei,Chen Jinfeng,Zhang Xiaoming
Abstract
Abstract
Background
MicroRNAs (miRNAs) and other epigenetic modifications play fundamental roles in all eukaryotic biological processes. DNA damage repair is a key process for maintaining the genomic integrity of different organisms exposed to diverse stresses. However, the reaction of miRNAs in the DNA damage repair process is unclear.
Results
In this study, we found that the simultaneous mutation of zinc finger DNA 3′-phosphoesterase (ZDP) and AP endonuclease 2 (APE2), two genes that play overlapping roles in active DNA demethylation and base excision repair (BER), led to genome-wide alteration of miRNAs. The transcripts of newly transcribed miRNA-encoding genes (MIRs) decreased significantly in zdp/ape2, indicating that the mutation of ZDP and APE2 affected the accumulation of miRNAs at the transcriptional level. In addition, the introduction of base damage with the DNA-alkylating reagent methyl methanesulfonate (MMS) accelerated the reduction of miRNAs in zdp/ape2. Further mutation of FORMAMIDOPYRIMIDINE DNA GLYCOSYLASE (FPG), a bifunctional DNA glycosylase/lyase, rescued the accumulation of miRNAs in zdp/ape2, suggesting that the accumulation of DNA damage repair intermediates induced the transcriptional repression of miRNAs.
Conclusions
Our investigation indicates that the accumulation of DNA damage repair intermediates inhibit miRNAs accumulation by inhibiting MIR transcriptions.
Funder
National Natural Science Foundation of China
Beijing Municipal Natural Science Foundation
Strategic Priority Research program of the CAS
the National Key Plan for Scientific Research and Development of China
Program of CAS
Open Research Fund Program of State Key Laboratory of Integrated Pest Management
Publisher
Springer Science and Business Media LLC
Cited by
2 articles.
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