Abstract
The origin licensing repressor geminin is a unique bifunctional protein providing a molecular link between cellular proliferation, differentiation and genomic stability. Here we report the first molecular structure of human geminin, determined by EM and image processing at a resolution of 17.5 Å. The geminin molecule is a tetramer formed by two dimers with monomers interacting via coiled-coil domains. The unusual structural organization of geminin provides molecular insight into its bifunctional nature.
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Acknowledgements
We thank A. Dutta for geminin cDNA and H. Saibil, D. Madge and D. Selwood for stimulating discussions and critical reading of the manuscript. This work has been funded by Cancer Research UK scientific programme grant SP2360/0103 (G.H.W. and K.S.) and by UK Biotechnology and Biological Sciences Research Council programme grant 31/SB09826 (A.L.O., E.V.O., C.B. and U.G.). S.R.K. is supported by a UK Medical Research Council studentship.
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Supplementary information
Supplementary Fig. 1
Biochemical properties of recombinant geminin. (PDF 279 kb)
Supplementary Fig. 2
Three-dimensional reconstruction of human geminin. (PDF 66 kb)
Supplementary Fig. 3
Properties of an N-terminal truncated form of human geminin and modeling of geminin's dimeric coiled coil domain. (PDF 92 kb)
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Okorokov, A., Orlova, E., Kingsbury, S. et al. Molecular structure of human geminin. Nat Struct Mol Biol 11, 1021–1022 (2004). https://doi.org/10.1038/nsmb835
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DOI: https://doi.org/10.1038/nsmb835
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