Alexander Gann

Jacob and Monod: From Operons to EvoDevo

Thanks to Sydney Brenner, Allan Campbell, Sean Carroll, Richard Ebright, Greg Hannon, Sandy Johnson, Mike Levine, Rich Losick, Rob Martienssen, Matt Meselson, Noreen Murray, Mark Ptashne and Gary Ruvkun.

What has phage lambda ever done for us

Shortly after the dawn of biochemical genetics, Escherichia coli K-12 replaced Neurospora crassa as the key model organism. With E. coli K-12 came another, even simpler, system: each bacterial cell contained a dormant virus (bacteriophage) called lambda (λ). Occasionally, the quiescent λ genome was activated to generate free phage particles. Thus it was discovered that phage λ propagates by two alternative pathways: lytic or lysogenic. In lysogeny, it is now known that the phage genome is integrated within the bacterial host genome and replicates passively along with it; in the lytic pathway, the λ genome replicates free from the bacterial genome, directs the production of phage capsid proteins, and kills its host to release some 100 or so new phage particles (Figure 1).

35 GAL11, GAL11P, and the Action of GAL4

OVERVIEW A transcriptional activator binds to DNA through a DNA-binding domain and activates transcription of a nearby gene through a separate activating region. According to the simplest version of this picture, both domains are located on a single polypeptide, but it is now clear that this is not always the case; we know of activators whose DNA-binding and activating regions, although working within the framework outlined above, are located on separate proteins which must both be present to activate transcription. Examples of activators with this and even more elaborate arrangements are discussed. In particular, we present a model for how the yeast activator GAL4 works in collaboration with GAL11 to produce a strong activator. INTRODUCTION GAL4 is an 881-amino-acid protein found in yeast that binds to specific DNA sequences and activates transcription of nearby genes. It contains a type of Zn-dependent DNA-binding domain at its amino-terminal end (Keegan et al. 1986; Johnston 1987; Pan and Coleman 1990) and two acidic activating regions (designated I and II in Fig. 1), either of which can activate transcription when fused to the DNA-binding domain (Ma and Ptashne 1987a). In yeast, the DNA-binding domain of GAL4 alone can bind to DNA but cannot activate transcription (Keegan et al. 1986; Ma and Ptashne 1987a; Sadowski et al. 1988; Gill et al. 1990), and a fusion protein bearing the activating regions of GAL4 attached to a heterologous DNA-binding domain, that of the bacterial repressor protein LexA, activates transcription when bound to Lex sites (Brent and Ptashne...

The lost correspondence of Francis Crick

Alexander Gann and Jan Witkowski unveil newly found letters between key players in the DNA story. Strained relationships and vivid personalities leap off the pages.

DNA: Archives reveal Nobel nominations

Recently released letters shed light on the Nobel prize nominations for the discovery of the DNA double helix 60 years ago. On 31 December 1961, Francis Crick sent Jacques Monod, at Monod’s request, a nine-page account of the discovery of the structure of DNA (see D. T. Zallen Nature 425, 15; 2003). Crick laid out what was known before work on the structure began in 1950, detailed his and James Watson’s contributions and summarized work confirming that their model was correct. Crick wrote, “I hope it [the account] is not far from the sort of thing you wanted. It really is most kind of you to take all this trouble on our behalf ” (source: Wellcome Library, London). This has been taken to mean that Monod was preparing to nominate Watson and Crick for the Nobel Prize in Physiology or Medicine, which they won in 1962 with Maurice Wilkins. Watson, in his 2007 book Avoid Boring People (Knopf) wrote: “Jacques Monod [...] could not keep secret from Francis Crick that a member of the Karolinska Institutet in Stockholm had asked him to nominate us in January for the 1962 Nobel Prize in Physiology or Medicine.” We were therefore surprised not to find Monod’s nomination letter among those released by the Nobel Committee for Physiology or Medicine. We found it instead in the archives of the Pasteur Institute in Paris, and, contrary to received wisdom, the nomination was for the prize in chemistry