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The cohesin complex: sequence homologies, interaction networks and shared motifs.

Jones S, Sgouros J - Genome Biol. (2001)

Bottom Line: We have combined genomic and proteomic data into a comprehensive network of information to reach a better understanding of the function of the cohesin complex.We have identified new SMC homologs, created a new SMC phylogeny and identified shared DNA and protein motifs.The potential for Scc2 to function as a kinase - a hypothesis that needs to be verified experimentally - could provide further evidence for the regulation of sister-chromatid cohesion by phosphorylation mechanisms, which are currently poorly understood.

View Article: PubMed Central - HTML - PubMed

Affiliation: Computational Genome Analysis Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK. Susan.Jones@icrf.icnet.uk

ABSTRACT

Background: Cohesin is a macromolecular complex that links sister chromatids together at the metaphase plate during mitosis. The links are formed during DNA replication and destroyed during the metaphase-to-anaphase transition. In budding yeast, the 14S cohesin complex comprises at least two classes of SMC (structural maintenance of chromosomes) proteins - Smc1 and Smc3 - and two SCC (sister-chromatid cohesion) proteins - Scc1 and Scc3. The exact function of these proteins is unknown.

Results: Searches of protein sequence databases have revealed new homologs of cohesin proteins. In mouse, Mmip1 (Mad member interacting protein 1) and Smc3 share 99% sequence identity and are products of the same gene. A phylogenetic tree of SMC homologs reveals five families: Smc1, Smc2, Smc3, Smc4 and an ancestral family that includes the sequences from the Archaea and Eubacteria. This ancestral family also includes sequences from eukaryotes. A cohesion interaction network, comprising 17 proteins, has been constructed using two proteomic databases. Genes encoding six proteins in the cohesion network share a common upstream region that includes the MluI cell-cycle box (MCB) element. Pairs of the proteins in this network share common sequence motifs that could represent common structural features such as binding sites. Scc2 shares a motif with Chk1 (kinase checkpoint protein), that comprises part of the serine/threonine protein kinase motif, including the active-site residue.

Conclusions: We have combined genomic and proteomic data into a comprehensive network of information to reach a better understanding of the function of the cohesin complex. We have identified new SMC homologs, created a new SMC phylogeny and identified shared DNA and protein motifs. The potential for Scc2 to function as a kinase - a hypothesis that needs to be verified experimentally - could provide further evidence for the regulation of sister-chromatid cohesion by phosphorylation mechanisms, which are currently poorly understood.

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Evolutionary tree for SMC proteins, created using PHYLIP [69,70]. Each of the five SMC families is highlighted and labeled. The names of the eukaryotic proteins present in the ancestral family are underlined. Bootstrap values from 100 bootstrap trials are shown on the primary branches of the tree. AQUAE, Aquifex aeolicus; ARATH, Arabidopsis thaliana; ARCFU, Archaeoglobus fulgidus; ASPN, Aspergillus niger; BACSU, Bacillus subtilis; CAEEL, Caenorhabditis elegans; CAUCR, Caulobacter crescentus; DROS, Drosophila; ECOLI, Escherichia coli; JAPPU, Japanese pufferfish; METJA, Methanococcus jannaschii; MUS,mouse; MYCGE, Mycoplasma genitalium; MYCHR, Mycoplasma hyorhinis; MYCPN, Mycoplasma pneumonia; PYRAB, Pyrococcus abyssii; PYRHO, Pyrococcus horikoshii; SCHP, Schizosaccharomyces pombe; SYNSP, Synechocystis sp.; THEMA, Thermotoga maritima; TREPA, Treponema pallidum; XENLA, XENO, Xenopus laevis; YEAST, Saccharomyces cerevisiae.
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Figure 2: Evolutionary tree for SMC proteins, created using PHYLIP [69,70]. Each of the five SMC families is highlighted and labeled. The names of the eukaryotic proteins present in the ancestral family are underlined. Bootstrap values from 100 bootstrap trials are shown on the primary branches of the tree. AQUAE, Aquifex aeolicus; ARATH, Arabidopsis thaliana; ARCFU, Archaeoglobus fulgidus; ASPN, Aspergillus niger; BACSU, Bacillus subtilis; CAEEL, Caenorhabditis elegans; CAUCR, Caulobacter crescentus; DROS, Drosophila; ECOLI, Escherichia coli; JAPPU, Japanese pufferfish; METJA, Methanococcus jannaschii; MUS,mouse; MYCGE, Mycoplasma genitalium; MYCHR, Mycoplasma hyorhinis; MYCPN, Mycoplasma pneumonia; PYRAB, Pyrococcus abyssii; PYRHO, Pyrococcus horikoshii; SCHP, Schizosaccharomyces pombe; SYNSP, Synechocystis sp.; THEMA, Thermotoga maritima; TREPA, Treponema pallidum; XENLA, XENO, Xenopus laevis; YEAST, Saccharomyces cerevisiae.

Mentions: The SMC phylogenetic tree created from the alignment of SMC3 homologs (Figure 2) reveals five families: Smc1-Smc4 from eukaryotes and a fifth 'ancestral' family that includes the SMCs from eubacteria and archaea. This ancestral family also includes a number of eukaryotic proteins from S. cerevisiae, Schizosaccharomyces pombe, Caenorhabditis elegans, Drosophila melanogaster and humans. Each of these eukaryotes has SMC proteins from all five families. The eukaryotic proteins within the ancestral family include the Rad18 from S. pombe and Rhc18, the Rad18 homolog in S. cerevisiae. Rad18 in S. pombe is involved in the repair of DNA damaged by UV radiation [19]. The sequences from C. elegans, Drosophila and human that cluster with Rad18 within the ancestral family are likely to be Rad18 homologs. Also clustered within this group is Spr18, an SMC protein proposed to be the homodimeric partner of rad18 in S. pombe [20]. In addition, MukB from Escherichia coli also lies within this ancestral family. MukB is known to be essential for chromosome partitioning in this species [21,22,23]. The clustering of the Rad18 homologs with the ancestral SMC proteins is not observed in the phylogenetic tree constructed by Cobbe and Heck [18].


The cohesin complex: sequence homologies, interaction networks and shared motifs.

Jones S, Sgouros J - Genome Biol. (2001)

Evolutionary tree for SMC proteins, created using PHYLIP [69,70]. Each of the five SMC families is highlighted and labeled. The names of the eukaryotic proteins present in the ancestral family are underlined. Bootstrap values from 100 bootstrap trials are shown on the primary branches of the tree. AQUAE, Aquifex aeolicus; ARATH, Arabidopsis thaliana; ARCFU, Archaeoglobus fulgidus; ASPN, Aspergillus niger; BACSU, Bacillus subtilis; CAEEL, Caenorhabditis elegans; CAUCR, Caulobacter crescentus; DROS, Drosophila; ECOLI, Escherichia coli; JAPPU, Japanese pufferfish; METJA, Methanococcus jannaschii; MUS,mouse; MYCGE, Mycoplasma genitalium; MYCHR, Mycoplasma hyorhinis; MYCPN, Mycoplasma pneumonia; PYRAB, Pyrococcus abyssii; PYRHO, Pyrococcus horikoshii; SCHP, Schizosaccharomyces pombe; SYNSP, Synechocystis sp.; THEMA, Thermotoga maritima; TREPA, Treponema pallidum; XENLA, XENO, Xenopus laevis; YEAST, Saccharomyces cerevisiae.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC30708&req=5

Figure 2: Evolutionary tree for SMC proteins, created using PHYLIP [69,70]. Each of the five SMC families is highlighted and labeled. The names of the eukaryotic proteins present in the ancestral family are underlined. Bootstrap values from 100 bootstrap trials are shown on the primary branches of the tree. AQUAE, Aquifex aeolicus; ARATH, Arabidopsis thaliana; ARCFU, Archaeoglobus fulgidus; ASPN, Aspergillus niger; BACSU, Bacillus subtilis; CAEEL, Caenorhabditis elegans; CAUCR, Caulobacter crescentus; DROS, Drosophila; ECOLI, Escherichia coli; JAPPU, Japanese pufferfish; METJA, Methanococcus jannaschii; MUS,mouse; MYCGE, Mycoplasma genitalium; MYCHR, Mycoplasma hyorhinis; MYCPN, Mycoplasma pneumonia; PYRAB, Pyrococcus abyssii; PYRHO, Pyrococcus horikoshii; SCHP, Schizosaccharomyces pombe; SYNSP, Synechocystis sp.; THEMA, Thermotoga maritima; TREPA, Treponema pallidum; XENLA, XENO, Xenopus laevis; YEAST, Saccharomyces cerevisiae.
Mentions: The SMC phylogenetic tree created from the alignment of SMC3 homologs (Figure 2) reveals five families: Smc1-Smc4 from eukaryotes and a fifth 'ancestral' family that includes the SMCs from eubacteria and archaea. This ancestral family also includes a number of eukaryotic proteins from S. cerevisiae, Schizosaccharomyces pombe, Caenorhabditis elegans, Drosophila melanogaster and humans. Each of these eukaryotes has SMC proteins from all five families. The eukaryotic proteins within the ancestral family include the Rad18 from S. pombe and Rhc18, the Rad18 homolog in S. cerevisiae. Rad18 in S. pombe is involved in the repair of DNA damaged by UV radiation [19]. The sequences from C. elegans, Drosophila and human that cluster with Rad18 within the ancestral family are likely to be Rad18 homologs. Also clustered within this group is Spr18, an SMC protein proposed to be the homodimeric partner of rad18 in S. pombe [20]. In addition, MukB from Escherichia coli also lies within this ancestral family. MukB is known to be essential for chromosome partitioning in this species [21,22,23]. The clustering of the Rad18 homologs with the ancestral SMC proteins is not observed in the phylogenetic tree constructed by Cobbe and Heck [18].

Bottom Line: We have combined genomic and proteomic data into a comprehensive network of information to reach a better understanding of the function of the cohesin complex.We have identified new SMC homologs, created a new SMC phylogeny and identified shared DNA and protein motifs.The potential for Scc2 to function as a kinase - a hypothesis that needs to be verified experimentally - could provide further evidence for the regulation of sister-chromatid cohesion by phosphorylation mechanisms, which are currently poorly understood.

View Article: PubMed Central - HTML - PubMed

Affiliation: Computational Genome Analysis Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK. Susan.Jones@icrf.icnet.uk

ABSTRACT

Background: Cohesin is a macromolecular complex that links sister chromatids together at the metaphase plate during mitosis. The links are formed during DNA replication and destroyed during the metaphase-to-anaphase transition. In budding yeast, the 14S cohesin complex comprises at least two classes of SMC (structural maintenance of chromosomes) proteins - Smc1 and Smc3 - and two SCC (sister-chromatid cohesion) proteins - Scc1 and Scc3. The exact function of these proteins is unknown.

Results: Searches of protein sequence databases have revealed new homologs of cohesin proteins. In mouse, Mmip1 (Mad member interacting protein 1) and Smc3 share 99% sequence identity and are products of the same gene. A phylogenetic tree of SMC homologs reveals five families: Smc1, Smc2, Smc3, Smc4 and an ancestral family that includes the sequences from the Archaea and Eubacteria. This ancestral family also includes sequences from eukaryotes. A cohesion interaction network, comprising 17 proteins, has been constructed using two proteomic databases. Genes encoding six proteins in the cohesion network share a common upstream region that includes the MluI cell-cycle box (MCB) element. Pairs of the proteins in this network share common sequence motifs that could represent common structural features such as binding sites. Scc2 shares a motif with Chk1 (kinase checkpoint protein), that comprises part of the serine/threonine protein kinase motif, including the active-site residue.

Conclusions: We have combined genomic and proteomic data into a comprehensive network of information to reach a better understanding of the function of the cohesin complex. We have identified new SMC homologs, created a new SMC phylogeny and identified shared DNA and protein motifs. The potential for Scc2 to function as a kinase - a hypothesis that needs to be verified experimentally - could provide further evidence for the regulation of sister-chromatid cohesion by phosphorylation mechanisms, which are currently poorly understood.

Show MeSH
Related in: MedlinePlus