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We have developed GoMiner, a program package that organizes lists of 'interesting' genes (for example, under- and overexpressed genes from a microarray experiment) for biological interpretation in the context of the Gene Ontology. GoMiner provides quantitative and statistical output files and two useful visualizations. The first is a tree-like structure(More)
Sir2 is a NAD+-dependent protein deacetylase that extends lifespan in yeast and worms. This study examines seven human proteins homologous to Sir2 (SIRT1 through SIRT7) for cellular localization, expression profiles, protein deacetylation activity, and effects on human cell lifespan. We found that: 1) three nuclear SIRT proteins (SIRT1, SIRT6, and SIRT7)(More)
The Sir2 histone deacetylase functions as a chromatin silencer to regulate recombination, genomic stability, and aging in budding yeast. Seven mammalian Sir2 homologs have been identified (SIRT1-SIRT7), and it has been speculated that some may have similar functions to Sir2. Here, we demonstrate that SIRT6 is a nuclear, chromatin-associated protein that(More)
The Sir2 deacetylase regulates chromatin silencing and lifespan in Saccharomyces cerevisiae. In mice, deficiency for the Sir2 family member SIRT6 leads to a shortened lifespan and a premature ageing-like phenotype. However, the molecular mechanisms of SIRT6 function are unclear. SIRT6 is a chromatin-associated protein, but no enzymatic activity of SIRT6 at(More)
Activation of telomerase is one of the rate-limiting steps in human cell immortalization and carcinogenesis. Human telomerase is composed of at least two protein subunits and an RNA component. Regulation of expression of the catalytic subunit, human telomerase reverse transcriptase (hTERT), is suggested as the major determinant of the enzymatic activity. We(More)
Primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates.(More)
The most common cause of primary autosomal recessive microcephaly (MCPH) appears to be mutations in the ASPM gene which is involved in the regulation of neurogenesis. The predicted gene product contains two putative N-terminal calponin-homology (CH) domains and a block of putative calmodulin-binding IQ domains common in actin binding cytoskeletal and(More)
Chromosomal aneuploidies are observed in essentially all sporadic carcinomas. These aneuploidies result in tumor-specific patterns of genomic imbalances that are acquired early during tumorigenesis, continuously selected for and faithfully maintained in cancer cells. Although the paradigm of translocation induced oncogene activation in hematologic(More)
A mammalian cell culture system using normal, diploid Syrian hamster embryo fibroblasts was used as a model to study the ability of diethylstilbestrol (DES) and related compounds to induce neoplastic transformation. Like benzo(a)pyrene, a known chemical carcinogen, DES (0.01 to 10 /ig/ml) induces morphological transformation of Syrian hamster embryo fibro(More)
BACKGROUND Microarrays for the analysis of gene expression are of three different types: short oligonucleotide (25-30 base), long oligonucleotide (50-80 base), and cDNA (highly variable in length). The short oligonucleotide and cDNA arrays have been the mainstay of expression analysis to date, but long oligonucleotide platforms are gaining in popularity and(More)