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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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The cohesion interaction network. Lines connecting proteins indicate known or potential interactions as derived from two proteomic databases and the literature. Cohesin and the loading factors are in yellow; additional proteins involved in cohesion or interacting with cohesin or the loading factors are in blue; all other proteins in the network are in white. Proteins outlined with boxes are part of macromolecular complexes. Prp11 is part of a complex in the spliceosomal pathway, and Apc2 is part of the anaphase-promoting complex (APC). Tid3p and Spc24 are both part of the spindle-pole body. Solid black lines indicate proteins that form dimeric interactions. The cohesion network of 17 proteins includes all those labeled, excluding Apc2, Tid4, Tid1 and Rad51.
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Figure 3: The cohesion interaction network. Lines connecting proteins indicate known or potential interactions as derived from two proteomic databases and the literature. Cohesin and the loading factors are in yellow; additional proteins involved in cohesion or interacting with cohesin or the loading factors are in blue; all other proteins in the network are in white. Proteins outlined with boxes are part of macromolecular complexes. Prp11 is part of a complex in the spliceosomal pathway, and Apc2 is part of the anaphase-promoting complex (APC). Tid3p and Spc24 are both part of the spindle-pole body. Solid black lines indicate proteins that form dimeric interactions. The cohesion network of 17 proteins includes all those labeled, excluding Apc2, Tid4, Tid1 and Rad51.

Mentions: A cohesion interaction network was created by collating information from two proteome databases and the literature (Figure 3). In Figure 3, lines are drawn between proteins to indicate known or potential interactions. The data from which the interactions are derived are indicated in a detailed key that differentiates between the two proteomic databases (and between the different sources of data within each database) and the literature. Four proteins (Esp1, Trf4, Prp11 and Tid3) interact directly with SMC or SCC proteins in S. cerevisiae. The interaction of Esp1 and Scc1 is currently known at a functional level [13], and its importance has already been discussed. This interaction is time-dependent and has not been identified in the yeast two-hybrid screen, and this information is not currently recorded in the YPD.


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

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

The cohesion interaction network. Lines connecting proteins indicate known or potential interactions as derived from two proteomic databases and the literature. Cohesin and the loading factors are in yellow; additional proteins involved in cohesion or interacting with cohesin or the loading factors are in blue; all other proteins in the network are in white. Proteins outlined with boxes are part of macromolecular complexes. Prp11 is part of a complex in the spliceosomal pathway, and Apc2 is part of the anaphase-promoting complex (APC). Tid3p and Spc24 are both part of the spindle-pole body. Solid black lines indicate proteins that form dimeric interactions. The cohesion network of 17 proteins includes all those labeled, excluding Apc2, Tid4, Tid1 and Rad51.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC30708&req=5

Figure 3: The cohesion interaction network. Lines connecting proteins indicate known or potential interactions as derived from two proteomic databases and the literature. Cohesin and the loading factors are in yellow; additional proteins involved in cohesion or interacting with cohesin or the loading factors are in blue; all other proteins in the network are in white. Proteins outlined with boxes are part of macromolecular complexes. Prp11 is part of a complex in the spliceosomal pathway, and Apc2 is part of the anaphase-promoting complex (APC). Tid3p and Spc24 are both part of the spindle-pole body. Solid black lines indicate proteins that form dimeric interactions. The cohesion network of 17 proteins includes all those labeled, excluding Apc2, Tid4, Tid1 and Rad51.
Mentions: A cohesion interaction network was created by collating information from two proteome databases and the literature (Figure 3). In Figure 3, lines are drawn between proteins to indicate known or potential interactions. The data from which the interactions are derived are indicated in a detailed key that differentiates between the two proteomic databases (and between the different sources of data within each database) and the literature. Four proteins (Esp1, Trf4, Prp11 and Tid3) interact directly with SMC or SCC proteins in S. cerevisiae. The interaction of Esp1 and Scc1 is currently known at a functional level [13], and its importance has already been discussed. This interaction is time-dependent and has not been identified in the yeast two-hybrid screen, and this information is not currently recorded in the YPD.

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