Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA.
Human thymine DNA glycosylase (hTDG) efficiently excises 5-carboxylcytosine (5caC), a key oxidation product of 5-methylcytosine in genomic DNA, in a recently discovered cytosine demethylation pathway. We present here the crystal structures of the hTDG catalytic domain in complex with duplex DNA containing either 5caC or a fluorinated analog. These structures, together with biochemical and computational analyses, reveal that 5caC is specifically recognized in the active site of hTDG, supporting the role of TDG in mammalian 5-methylcytosine demethylation.
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA.
Liang
L
Zhang
Xingyu
X
Lu
Junyan
J
Lu
Haihua
H
Liang
Qing
Q
Dai
Guo-Liang
GL
Xu
Cheng
C
Luo
Hualiang
H
Jiang
Chuan
C
He
D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D019175:DNA Methylation; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D044502:Thymine DNA Glycosylase / Q000737:chemistry* / Q000378:metabolism*
C560974:5-carboxylcytosine; D003596:Cytosine; D004247:DNA; D044502:Thymine DNA Glycosylase