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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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Sequence alignments for three motifs shared by proteins in the cohesion network. (a) A motif shared by Scc2 and Trf4 in the network and a putative seryl-tRNA synthetase (YHH1) from yeast. (b) A motif shared by Scc1, Smc1 and a P-type ATPase from Plasmodium yoelii. (c) A motif shared by the cohesin loading factor Scc4 and SMC3. In each alignment the conserved residues of the motif identified using Teiresias are in red and additional conserved positions are in green. The number before each motif indicates the position of the first residue within the complete sequence.
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Figure 5: Sequence alignments for three motifs shared by proteins in the cohesion network. (a) A motif shared by Scc2 and Trf4 in the network and a putative seryl-tRNA synthetase (YHH1) from yeast. (b) A motif shared by Scc1, Smc1 and a P-type ATPase from Plasmodium yoelii. (c) A motif shared by the cohesin loading factor Scc4 and SMC3. In each alignment the conserved residues of the motif identified using Teiresias are in red and additional conserved positions are in green. The number before each motif indicates the position of the first residue within the complete sequence.

Mentions: A second motif shared by a third protein not included in the cohesion network was SXXSXLKKKXLXT; this is found in Scc1, Scc2 and yeast ORF YHR011W, a putative seryl-tRNA synthetase (Figure 5a). However, this motif was not part of the tRNA ligase motif of YHR011W, or of any other known motif within this sequence. A third motif shared by a protein from outside the cohesion network was NDXNXDDXDN, shared by Scc1, Smc1, and a P-type ATPase from Plasmodium yoelii (Figure 5b). Scc4 is one of the cohesin loading factors for which no known homolog has been found. This protein was, however, found to share a 10-residue sequence motif (GKXVALTNAK) with Smc3 (Figure 5c).


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

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

Sequence alignments for three motifs shared by proteins in the cohesion network. (a) A motif shared by Scc2 and Trf4 in the network and a putative seryl-tRNA synthetase (YHH1) from yeast. (b) A motif shared by Scc1, Smc1 and a P-type ATPase from Plasmodium yoelii. (c) A motif shared by the cohesin loading factor Scc4 and SMC3. In each alignment the conserved residues of the motif identified using Teiresias are in red and additional conserved positions are in green. The number before each motif indicates the position of the first residue within the complete sequence.
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Related In: Results  -  Collection

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Figure 5: Sequence alignments for three motifs shared by proteins in the cohesion network. (a) A motif shared by Scc2 and Trf4 in the network and a putative seryl-tRNA synthetase (YHH1) from yeast. (b) A motif shared by Scc1, Smc1 and a P-type ATPase from Plasmodium yoelii. (c) A motif shared by the cohesin loading factor Scc4 and SMC3. In each alignment the conserved residues of the motif identified using Teiresias are in red and additional conserved positions are in green. The number before each motif indicates the position of the first residue within the complete sequence.
Mentions: A second motif shared by a third protein not included in the cohesion network was SXXSXLKKKXLXT; this is found in Scc1, Scc2 and yeast ORF YHR011W, a putative seryl-tRNA synthetase (Figure 5a). However, this motif was not part of the tRNA ligase motif of YHR011W, or of any other known motif within this sequence. A third motif shared by a protein from outside the cohesion network was NDXNXDDXDN, shared by Scc1, Smc1, and a P-type ATPase from Plasmodium yoelii (Figure 5b). Scc4 is one of the cohesin loading factors for which no known homolog has been found. This protein was, however, found to share a 10-residue sequence motif (GKXVALTNAK) with Smc3 (Figure 5c).

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