Abstract
The structural maintenance of chromosomes (SMC) protein encoded by the fission yeast rad18 gene is involved in several DNA repair processes and has an essential function in DNA replication and mitotic control. It has a heterodimeric partner SMC protein, Spr18, with which it forms the core of a multiprotein complex. We have now isolated the human orthologues of rad18 and spr18 and designated them hSMC6 and hSMC5. Both proteins are about 1100 amino acids in length and are 27-28% identical to their fission yeast orthologues, with much greater identity within their N- and C-terminal globular domains. The hSMC6 and hSMC5 proteins interact to form a tight complex analogous to the yeast Rad18/Spr18 heterodimer. In proliferating human cells the proteins are bound to both chromatin and the nucleoskeleton. In addition, we have detected a phosphorylated form of hSMC6 that localizes to interchromatin granule clusters. Both the total level of hSMC6 and its phosphorylated form remain constant through the cell cycle. Both hSMC5 and hSMC6 proteins are expressed at extremely high levels in the testis and associate with the sex chromosomes in the late stages of meiotic prophase, suggesting a possible role for these proteins in meiosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Blotting, Northern
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Blotting, Western
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Cell Cycle Proteins / chemistry*
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Cell Cycle Proteins / metabolism
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Cell Division
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Cell Line
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Cell Line, Transformed
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Cell Nucleus / metabolism
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Cells, Cultured
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Chromatin / metabolism
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Chromosomal Proteins, Non-Histone / chemistry
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Chromosomal Proteins, Non-Histone / metabolism*
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Cloning, Molecular
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DNA, Complementary / metabolism
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / metabolism*
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Dimerization
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Fibroblasts / metabolism
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Fungal Proteins / chemistry*
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Humans
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Meiosis
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Mice
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Microscopy, Fluorescence
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Molecular Sequence Data
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Phosphoric Monoester Hydrolases / metabolism
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Phosphorylation
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Protein Binding
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Protein Structure, Tertiary
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Saccharomyces cerevisiae Proteins*
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Schizosaccharomyces / chemistry*
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Schizosaccharomyces pombe Proteins*
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Sequence Homology, Amino Acid
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Tissue Distribution
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Ubiquitin-Protein Ligases
Substances
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Cell Cycle Proteins
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Chromatin
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Chromosomal Proteins, Non-Histone
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DNA, Complementary
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DNA-Binding Proteins
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Fungal Proteins
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RAD18 protein, S cerevisiae
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RAD18 protein, human
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SMC5 protein, human
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SMC6 protein, human
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Saccharomyces cerevisiae Proteins
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Schizosaccharomyces pombe Proteins
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Smc5 protein, S pombe
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smc6 protein, S pombe
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Ubiquitin-Protein Ligases
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Phosphoric Monoester Hydrolases