title: Real time in vitro regulation of DNA methylation using a 5-fluorouracil conjugated DNA-based stimuli-responsive platform.
abstract: DNA methylation, catalyzed by methylases, plays a critical role in many biological processes, and many methylases have been regarded as promising targets for antimicrobial drugs. In this work, we report a stimulus responsive, self-regulating anticancer drug release platform, comprising a multifunctional DNA that upon methylation by methyltransferase (MTase) releases 5-fluorouracil (5-Fu) and in turn inhibits subsequent expression of MTase. The multifunctional DNA with anticancer drug are first methylated by DNA adenine methylation (DAM) methyltransferase (MTase) and then cut by the methylation-sensitive restriction endonuclease Dpn I. Removal of duplex from the functional DNA by the methylation/cleavage process will release the anticancer drug, resulting in inhibition of the activity of DAM in turn. Consequently, the enzyme activity of DAM MTase can be self-regulated. Furthermore, we found that the inhibition efficiency of 5-Fu significantly increase as it is functionalized with DNA.
authors.affiliation: Laboratory of Physical Biology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xiuhai
authors.initials: X
authors.lastname: Mao
authors.forename: Ming
authors.initials: M
authors.lastname: Wei
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Zhu
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lu
authors.forename: Jimin
authors.initials: J
authors.lastname: Gao
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Simon
authors.forename: Jiye
authors.initials: J
authors.lastname: Shi
authors.forename: Qing
authors.initials: Q
authors.lastname: Huang
authors.forename: Chunhai
authors.initials: C
authors.lastname: Fan
mesh_terms: D000225:Adenine / Q000737:chemistry / Q000378:metabolism; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry; D002232:Carbocyanines / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D019175:DNA Methylation; D004262:DNA Restriction Enzymes / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism; D005472:Fluorouracil / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002232:Carbocyanines; D004277:DNA, Single-Stranded; C089187:cyanine dye 3; D004247:DNA; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D004262:DNA Restriction Enzymes; D000225:Adenine; D005472:Fluorouracil