William Wells
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Articles by William Wells

Many ways to be minimal
William Wells | | 1 min read
The genome of Mycoplasma genitalium is so far the smallest discovered for any free-living organism, so it has been used as a starting point for defining a minimal genome. Transposon mutagenesis and comparison with a second mycoplasma have further narrowed down the list of genes. Now Glass et al. announce the sequencing of a third mycoplasma, the mucosal pathogen Ureaplasma urealyticum, in the 12 October Nature (Nature 2000, 407:757-762). Their results suggest that there is more than one version

Gene therapy with histones
William Wells | | 1 min read
In the October 10 Proceedings of the National Academy of Sciences, Balicki et al. report that histone H2A can be used to increase the efficacy of gene therapy (Proc Natl Acad Sci USA 2000, 97:11500-11504). Histone H2A has been used in the past to coat DNA prior to transfection. It appears to work both because of its positive charge and some other property, which is presumed to be its nuclear-localizing activity. Balicki et al. use H2A for in vitro delivery of the gene for interleukin-2 (IL-2) to

Screening with X-rays
William Wells | | 1 min read
In the October Nature Biotechnology, Nienaber et al. demonstrate that drug or inhibitor leads can be identified by high throughput X-ray crystallography (Nat. Biotech. 2000, 18:1105-1108). Pre-formed protein crystals are soaked in solvents containing mixtures of 100 compounds before the crystals are examined by X-ray crystallography. Nienaber et al. look for changes in the electron-density map caused by ligand binding. The compounds in each mixture are chosen to be diverse in shape so that they

Watch out for the neighbors
William Wells | | 1 min read
Radiation induces DNA breaks, leading to chromosomal rearrangements. But do the breaks come first, followed by a wandering through the nucleus to find a suitable partner for the free DNA end? Or is the partner already nearby at the time of the break? In the 6 October Science, Nikiforova et al. provide evidence for the latter theory (Science 2000, 290:138-141). They look at papillary thyroid cancer, in which a radiation-induced inversion often fuses the genes for H4 and the RET receptor tyrosine

Prion-driven evolution
William Wells | | 1 min read
The yeast protein Sup35 is essential for translation termination, but its prion [PSI+] form reduces the fidelity of the termination process. Conversion of Sup35 into the prion form could therefore alter the sequence of multiple proteins at the same time, perhaps providing an engine for evolutionary change. In the 28 September Nature, True and Lindquist find that in nearly half of a long list of culture conditions tested, the presence of [PSI+] exerted a substantial effect on strain growth (Natur

SNPing away
William Wells | | 1 min read
In the 28 September Nature Altshuler et al. (Nature 2000, 407:513-516) and Mullikin et al. (Nature 2000, 407:516-520) report on the discovery of thousands of single nucleotide polymorphisms (SNPs). These human sequence variants, in which two alternate bases occur at one position, are present at a frequency of up to one per kilobase. A dense map of SNPs would allow certain variants to be associated with disease states. Previous efforts to uncover SNPs have struggled with the effort involved in am

in vitro
William Wells | | 1 min read
Cloning works because even highly differentiated somatic nuclei can de-differentiate and reacquire their ability to form all the cells of the body. The de-differentiation process is driven by egg cytoplasm, and in the 29 September Science Kikyo et al. report that the chromatin remodeling protein ISW1 is probably one component of the de-differentiation machinery (Science 2000, 289:2360-2362). Kikyo et al. identify a number of proteins that are released from permeabilized frog somatic nuclei only

A worm germline parts list
William Wells | | 1 min read
The sequencing of the genome of the worm Caenorhabditis elegans has made real worm genomics possible. In the September Molecular Cell, Reinke et al. make good on that promise with a DNA array analysis of 11,917 worm genes (~63% of the genome Mol. Cell 2000, 6:605-616). They define 1,416 genes whose transcription is enriched 1.8- to 104-fold in the worm germline, including 650 sperm-enriched genes, 258 oocyte-enriched genes, and 508 germline-intrinsic genes. Some genes can be picked out of this m

Sequence of a single-celled vulture
William Wells | | 1 min read
Thermoplasma acidophilum is an archaeon that lives off the carcasses of organisms that perish in its hot, acidic home. In the 28 September Nature, Ruepp et al. find that the microbe has scavenged genes from its neighbors in order to survive (Nature 2000, 407:508-513). T. acidophilum was originally suspected to be an ancestor of the eukaryotes, as it has complexes involved in protein folding, degradation and turnover that look like simplified versions of the corresponding eukaryotic complexes. Bu

A protein kinase switch
William Wells | | 1 min read
Kinase inhibitors are plagued by a lack of specificity. Now in the 21 September Nature Bishop et al. tackle the problem by building on their earlier work, in which they modified the ATP-binding sites of Src-family tyrosine kinases to accept either nucleotide analogs or modified kinase inhibitors. In the new work the researchers mutate kinases from four distinct kinase families by replacing a bulky residue with a small residue. This change provides enough room for the binding of inhibitor analogs

Hedgehogs make both fish and fly eyes
William Wells | | 1 min read
The fly eye is patterned by a morphogenetic wave driven by the Hedgehog signaling protein. In the 22 September Science Neumann and Nuesslein-Volhard report that neuronal differentiation in zebrafish eyes is dependent on a similar wave of hedgehog proteins (Science 2000, 289:2137-2139). Previous work on Pax6 already indicated that the mechanism of eye induction is conserved across the animal kingdom. But variations in eye structure suggested that events downstream of eye induction must have evolv

Chromodomains bind RNA
William Wells | | 1 min read
Male flies compensate for having a single X chromosome by doubling the single X chromosome's level of expression. This increase is mediated by MOF, a histone H4 acetyltransferase. MOF, along with other proteins and an RNA called roX2, binds to the male X chromosome. In the 21 September Nature Akhtar et al. find that MOF and another dosage compensation protein called MSL-3 use their chromodomains to bind to roX2 and thus to the male X (Nature 2000, 407:405-409). Other chromodomain proteins, which











