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  • Structure Watch
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Structure watch

Nature Reviews Molecular Cell Biology volume 12, page 74 (2011)Cite this article

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Mammalian CpG methylation must be faithfully reproduced when DNA is replicated to ensure that gene expression patterns are accurately inherited when cells divide. Maintenance DNA methylation is catalysed by DNA methyltransferase 1 (DNMT1), which has high affinity for hemi-methylated DNA; this allows it to recognise methylation on the parent DNA strand and copy it to the newly synthesized daughter strand. Now, Song et al. have used X-ray crystallography to show that unmethylated DNA is occluded from the active site of DNMT1, thus explaining how DNMT1 is specific for hemi-methylated DNA.

They solved a crystal structure of mouse DNMT1 in complex with unmethylated DNA at 3 Å resolution and showed that when the CXXC domain of DNMT1 binds to unmethylated DNA the protein conformation is altered such that the CXXC–bromo-adjacent homology 1 (BAH1) linker blocks access of the methyltransferase active site to the DNA. In addition, the target recognition domain of DNMT1 becomes stabilized in a retracted position, preventing it from interacting with the unmethylated DNA. This autoinhibitory mechanism prevents DNMT1 from introducing aberrant de novo methylation and thereby promotes accurate replication of DNA methylation patterns.

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ORIGINAL RESEARCH PAPERS

  1. Song, J. et al. Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation. Science 16 Dec 2010 (doi: 10.1126/science.1195380)

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  2. Buschhorn, B. A. et al. Substrate binding on the APC/C occurs between the coactivator Cdh1 and the processivity factor Doc1. Nature Struct. Mol. Biol. 18, 6–13 (2011)

    Article  CAS  Google Scholar 

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Structure watch. Nat Rev Mol Cell Biol 12, 74 (2011). https://doi.org/10.1038/nrm3057

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