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In eukaryotes, DNA replication requires the origin recognition complex (ORC), a six-subunit assembly that promotes replisome formation on chromosomal origins. Despite extant homology between certain subunits, the degree of structural and organizational overlap between budding yeast and metazoan ORC has been unclear. Using 3D electron microscopy, we determined the subunit organization of metazoan ORC, revealing that it adopts a global architecture very similar to the budding yeast complex. Bioinformatic analysis extends this conservation to Orc6, a subunit of somewhat enigmatic function. Unexpectedly, a mutation in the Orc6 C-terminus linked to Meier-Gorlin syndrome, a dwarfism disorder, impedes proper recruitment of Orc6 into ORC; biochemical studies reveal that this region of Orc6 associates with a previously uncharacterized domain of Orc3 and is required for ORC function and MCM2-7 loading in vivo. Together, our results suggest that Meier-Gorlin syndrome mutations in Orc6 impair the formation of ORC hexamers, interfering with appropriate ORC functions. DOI:http://dx.doi.org/10.7554/eLife.00882.001.
Pubmed ID: 24137536
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Non-profit academic organization for research and services in bioinformatics. Provides freely available data from life science experiments, performs basic research in computational biology, and offers user training programme, manages databases of biological data including nucleic acid, protein sequences, and macromolecular structures. Part of EMBL.
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View all literature mentionsRepository for electron microscopy density maps of macromolecular complexes and subcellular structures at Protein Data Bank in Europe. Covers techniques, including single-particle analysis, electron tomography, and electron (2D) crystallography.
View all literature mentionsPublic global Protein Data Bank archive of macromolecular structural data overseen by organizations that act as deposition, data processing and distribution centers for PDB data. Members are: RCSB PDB (USA), PDBe (Europe) and PDBj (Japan), and BMRB (USA). This site provides information about services provided by individual member organizations and about projects undertaken by wwPDB. Data available via websites of its member organizations.
View all literature mentionsSoftware package as multiple alignment program for amino acid or nucleotide sequences. Can align up to 500 sequences or maximum file size of 1 MB. First version of MAFFT used algorithm based on progressive alignment, in which sequences were clustered with help of Fast Fourier Transform. Subsequent versions have added other algorithms and modes of operation, including options for faster alignment of large numbers of sequences, higher accuracy alignments, alignment of non-coding RNA sequences, and addition of new sequences to existing alignments.
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