The cohesin complex: sequence homologies, interaction networks and shared motifs.
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.
Jones
S
S
Computational Genome Analysis Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK. Susan.Jones@icrf.icnet.uk
Sgouros
J
J
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000071877:Checkpoint Kinase 1; D011508:Chondroitin Sulfate Proteoglycans; D002842:Chromatids / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology; D016384:Consensus Sequence / Q000235:genetics; D019992:Databases as Topic; D029721:Drosophila Proteins; D005656:Fungal Proteins; D023281:Genomics; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins; D010766:Phosphorylation; D010802:Phylogeny; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D020543:Proteome; D020218:Response Elements / Q000235:genetics; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D017385:Sequence Homology; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000097722:Cohesins
D018797:Cell Cycle Proteins; D000071877:Checkpoint Kinase 1; D011508:Chondroitin Sulfate Proteoglycans; D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D005656:Fungal Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011494:Protein Kinases; D020543:Proteome; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000097722:Cohesins; C492317:SMC3 protein, mouse; C490529:MCD1 protein, S cerevisiae; C114087:SA protein, Drosophila; C120372:SMC3 protein, S cerevisiae; C492318:SMC3 protein, human; C000605867:CHEK1 protein, human; C000605869:Chek1 protein, mouse