GADD45A does not promote DNA demethylation.
Although DNA methylation patterns in somatic cells are thought to be relatively stable, they undergo dramatic changes during embryonic development, gametogenesis, and during malignant transformation. The enzymology of DNA methyltransferases is well understood, but the mechanism that removes methylated cytosines from DNA (active DNA demethylation) has remained enigmatic. Recently, a role of the growth arrest and DNA damage inducible protein GADD45A in DNA demethylation has been reported [1]. We have investigated the function of GADD45A in DNA demethylation in more detail using gene reactivation and DNA methylation assays. Contrary to the previous report, we were unable to substantiate a functional role of GADD45A in DNA demethylation. The mechanism of active DNA demethylation in mammalian cells remains unknown.
Jin
Seung-Gi
SG
Division of Biology, Beckman Research Institute of the City of Hope, Duarte, California, United States of America.
Guo
Cai
C
Pfeifer
Gerd P
GP
D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011247:Pregnancy; D011994:Recombinant Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D015053:Zygote / Q000378:metabolism; D000099250:DNA Excision Repair Protein ERCC-5; D000097642:GADD45 Proteins
D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D004720:Endonucleases; D049452:Green Fluorescent Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C499072:Gadd45a protein, mouse; C485184:enhanced green fluorescent protein