摘要It has been hypothesized that DNA damage has the potential to induce DNA hypermethylation,contributing to carcinogenesis in mammals.However,there is no sufficient evidence to support that DNA damage can cause genome-wide DNA hypermethylation.In this study,we demonstrated that DNA single-strand breaks with 3'blocked ends(DNA 3'blocks)not only can reinforce DNA methylation at normally methylated loci but also can induce DNA methylation at normally nonmethylated loci in plants.The CG and CHG hypermethy-lation tend to localize within gene bodies,with a significant proportion being de novo generated.In contrast,the CHH hypermethylation is concentrated in centromeric and pericentromeric regions,primarily being reinforced methylation.Mechanistically,DNA 3'blocks regulate the DREAM complex to induce CG and CHG methylation.Moreover,they utilize the RdDM pathway to induce CHH hypermethylation.Intrigu-ingly,repair of DNA damage or blocking the DNA damage response can fully abolish CHH hypermethylation and partially rescue CHG hypermethylation but rarely alter CG hypermethylation,indicating that DNA damage-induced symmetric DNA methylation can serve as a form of genetic imprinting.Collectively,these results suggest that DNA damage is an important force driving the emergence and evolution of genomic DNA methylation levels and patterns in plants.
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