Cold Spring Harbor Laboratory

About: Cold Spring Harbor Laboratory is a nonprofit organization based out in Cold Spring Harbor, New York, United States. It is known for research contribution in the topics: Gene & Genome. The organization has 3772 authors who have published 6603 publications receiving 1010873 citations. The organization is also known as: CSHL.

Ensembl comparative genomics resources

Abstract: Evolution provides the unifying framework with which to understand biology. The coherent investigation of genic and genomic data often requires comparative genomics analyses based on whole-genome alignments, sets of homologous genes and other relevant datasets in order to evaluate and answer evolutionary-related questions. However, the complexity and computational requirements of producing such data are substantial: this has led to only a small number of reference resources that are used for most comparative analyses. The Ensembl comparative genomics resources are one such reference set that facilitates comprehensive and reproducible analysis of chordate genome data. Ensembl computes pairwise and multiple whole-genome alignments from which large-scale synteny, per-base conservation scores and constrained elements are obtained. Gene alignments are used to define Ensembl Protein Families, GeneTrees and homologies for both protein-coding and non-coding RNA genes. These resources are updated frequently and have a consistent informatics infrastructure and data presentation across all supported species. Specialized web-based visualizations are also available including synteny displays, collapsible gene tree plots, a gene family locator and different alignment views. The Ensembl comparative genomics infrastructure is extensively reused for the analysis of non-vertebrate species by other projects including Ensembl Genomes and Gramene and much of the information here is relevant to these projects. The consistency of the annotation across species and the focus on vertebrates makes Ensembl an ideal system to perform and support vertebrate comparative genomic analyses. We use robust software and pipelines to produce reference comparative data and make it freely available. Database URL: http://www.ensembl.org.

Identity of the 19S 'prosome' particle with the large multifunctional protease complex of mammalian cells (the proteasome).

Abstract: There have been many reports that eukaryotic cells contain ring-shaped 19S or 20S particles which are composed of numerous polypeptide subunits ranging in size between 25 and 35 kilodaltons. Because these particles seemed to copurify with inactive mRNA, they were assumed to function in regulating mRNA translation and hence were named 'prosomes' (for 'programmed-o-some'). A number of properties have been reported for these structures, including an association with specific RNA species or with certain heat-shock proteins and involvement in tRNA processing or aminoacyl tRNA synthesis. However, these proposed activities have not been supported by definitive evidence. During studies of the proteolytic systems in mammalian tissues, we noted many similarities between these 19S particles and the high molecular weight protease complexes that are present in most or all eukaryotic cells. This (700 kilodalton) enzyme complex, designated here as LAMP for 'large alkaline multi-functional protease', contains three distinct endoproteolytic sites which function at neutral or alkaline pH and are specific for hydrolysis of proteins, hydrophobic peptides, or basic peptides. This protease also exists in a latent form which can be activated by polylysine, fatty acids, or ATP. In this report, we show that the prosomes and these protease complexes are very similar or identical with respect to their size, polypeptide composition, immunological cross-reactivity, appearance in the electron microscope, radial symmetry of subunits, subcellular localization, and proteolytic activities. Therefore, the 'prosome' probably plays a critical role in intracellular protein breakdown, and we propose that it be renamed 'proteasome'.

Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth

Abstract: There are about 800 genes in Saccharomyces cerevisiae whose transcription is cell-cycle regulated. Some of these form clusters of co-regulated genes. The 'CLB2' cluster contains 33 genes whose transcription peaks early in mitosis, including CLB1, CLB2, SWI5, ACE2, CDC5, CDC20 and other genes important for mitosis. Here we find that the genes in this cluster lose their cell cycle regulation in a mutant that lacks two forkhead transcription factors, Fkh1 and Fkh2. Fkh2 protein is associated with the promoters of CLB2, SWI5 and other genes of the cluster. These results indicate that Fkh proteins are transcription factors for the CLB2 cluster. The fkh1 fkh2 mutant also displays aberrant regulation of the 'SIC1' cluster, whose member genes are expressed in the M-G1 interval and are involved in mitotic exit. This aberrant regulation may be due to aberrant expression of the transcription factors Swi5 and Ace2, which are members of the CLB2 cluster and controllers of the SIC1 cluster. Thus, a cascade of transcription factors operates late in the cell cycle. Finally, the fkh1 fkh2 mutant displays a constitutive pseudohyphal morphology, indicating that Fkh1 and Fkh2 may help control the switch to this mode of growth.