N^(6)-methyldeoxyadenosine(6 mdA) modification is considered as a new epigenetic mark that may play important roles in various biological processes.However,it remains unclear about the effect of 6 mdA on DNA replicati...N^(6)-methyldeoxyadenosine(6 mdA) modification is considered as a new epigenetic mark that may play important roles in various biological processes.However,it remains unclear about the effect of 6 mdA on DNA replication in human cells.Herein,we combined next-generation sequencing with shuttle vector technology to explore how 6 mdA affects the efficiency and accuracy of DNA replication in human cells.Our results showed that 6 mdA neither blocked DNA replication nor induced mutations in human cells.Moreover,we found that the depletion of translesion synthesis DNA polymerase(Pol) κ,Pol η,Pol ι or Pol ζ did not significantly change the biological consequences of 6 mdA during replication in human cells.The negligible impact of 6 mdA on DNA replication is consistent with its potential role in epigenetic gene expression.展开更多
DNA methylation represents a major type of DNA modifications that play key roles in diverse biological processes.With the recent development of highly selective and sensitive bioanalytical techniques,N^(6)-methyladeni...DNA methylation represents a major type of DNA modifications that play key roles in diverse biological processes.With the recent development of highly selective and sensitive bioanalytical techniques,N^(6)-methyladenine(6mA)has been characterized as an important internal DNA modification dynamically occurring in multiple eukaryotes including humans.Increasing evidence has indicated that 6mA may act as a novel epigenetic modification involved in regulation of development,stress response and diseases such as cancer and neurodegenerative disorders.We review herein the recent advances in the detection and functional studies of 6mA modification,with special emphasis on its biological consequences and human health relevance as well as its dynamic regulation by various types of methyltransferases,demethylases and 6mA-binding proteins.It can be envisaged that further chemical and biological studies of 6mA modification will lead to a better understanding about its potentially important roles in normal and pathological biological processes.展开更多
基金supported by the National Natural Science Foundation of China (Nos. 21807030, 21907028)the Science and Technology Innovation Program of Hunan Province(No. 2019RS2020)+1 种基金Natural Science Foundation of Hunan Province(No. 2020JJ5046)the Fundamental Research Funds for the Central Universities (Nos. 531118010061, 531118010259)。
文摘N^(6)-methyldeoxyadenosine(6 mdA) modification is considered as a new epigenetic mark that may play important roles in various biological processes.However,it remains unclear about the effect of 6 mdA on DNA replication in human cells.Herein,we combined next-generation sequencing with shuttle vector technology to explore how 6 mdA affects the efficiency and accuracy of DNA replication in human cells.Our results showed that 6 mdA neither blocked DNA replication nor induced mutations in human cells.Moreover,we found that the depletion of translesion synthesis DNA polymerase(Pol) κ,Pol η,Pol ι or Pol ζ did not significantly change the biological consequences of 6 mdA during replication in human cells.The negligible impact of 6 mdA on DNA replication is consistent with its potential role in epigenetic gene expression.
基金supported by the National Natural Science Foun-dation of China(Nos.21807030,21907028)the Science and Tech-nology Innovation Program of Hunan Province(No.2019RS2020),Natural Science Foundation of Hunan Province(No.2020JJ5046)the Fundamental Research Funds for the Central Universities(Nos.531118010061,531118010259).
文摘DNA methylation represents a major type of DNA modifications that play key roles in diverse biological processes.With the recent development of highly selective and sensitive bioanalytical techniques,N^(6)-methyladenine(6mA)has been characterized as an important internal DNA modification dynamically occurring in multiple eukaryotes including humans.Increasing evidence has indicated that 6mA may act as a novel epigenetic modification involved in regulation of development,stress response and diseases such as cancer and neurodegenerative disorders.We review herein the recent advances in the detection and functional studies of 6mA modification,with special emphasis on its biological consequences and human health relevance as well as its dynamic regulation by various types of methyltransferases,demethylases and 6mA-binding proteins.It can be envisaged that further chemical and biological studies of 6mA modification will lead to a better understanding about its potentially important roles in normal and pathological biological processes.
