PerspectiveMolecular Biology

Preference by Exclusion

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Science  25 Feb 2011:
Vol. 331, Issue 6020, pp. 1017-1018
DOI: 10.1126/science.1202090

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DNA methylation is a modification that controls gene expression and contributes to mammalian development, aging, and cancer cell biology (1, 2). In mice and humans, the addition of a methyl group to a cytosine within a cytosine-guanine (CG) dinucleotide is catalyzed by DNA methyltransferase (DNMT) enzymes DNMT3A, DNMT3B, or DNMT1. The latter is the main “maintenance methylase” because it adds a methyl group primarily to double-strand DNA that is already methylated on one strand (hemimethylated). How DNMT1 prefers hemimethylated over unmethylated DNA, in contrast to DNMT3A and DNMT3B, has not been clear. On page 1036 of this issue, Song et al. (3) present the crystal structures of human and mouse DNMT1 in complex with unmethylated DNA, providing an explanation for the mechanism of substrate selection by this crucial enzyme.