Research On The Role And Mechanism Of ATM Gene In Somatic Cells Reprogramming

ATM(mutated in Ataxia-Telangiectasia)as an important serine-threonine protein kinase gene involved in DNA damage and repair.DNA double strand breaks can cause ATM activation,triggering a series of downstream damage repair reactions.In addition,the highly dynamic changes in chromosomes also activate ATM,iPS cells in the process of induction of chromosomes will be a great change and a high degree of modification,but few studies reported the role of ATM gene in the process of reprogramming.In this study,gene knockout techniques were used to analyze the effects of protease and protein kinase involved in cell metabolism and life activity on somatic cell reprogramming.The results showed that the induction efficiency of iPS cells was improved after knockdown of other phosphorylation related genes except chuk gene.Among them,the knockdown of ATM not only improve the efficiency of iPS induction,while the iPS cloning obtained a very good refraction,clear boundaries,and the formation of very different transdifferentiated cells,iPS cloning is very uniform.Further analysis showed that the reprogramming efficiency was reduced with the increase in the proportion of knockdown ATM,and the resulting clone endogenous Oct4 was not activated and could not continue to pass the passage,whereas the low knockdown ATM cloning was reprogrammed intact Functional gene expression is normal.In addition,inhibition of P53 and H2AX phosphorylation,and found that knock down ATM,and autophagy-related protein LC3 is activated,cell autophagy in the process of reprogramming also play an important role.Finally,we conclude that proper knockdown of ATM improves the reprogramming efficiency by reducing the level of P53-pi and yH2AX.