Volume 22 Issue 12, December 2012

Proper control of intercellular communication through the Wnt signaling pathway is of critical importance for many aspects of biology, including head formation during vertebrate embryogenesis. A recent Cell paper describes the discovery of a novel protein, TIKI, which controls head size through a surprising new mechanism of Wnt antagonism.

The laboratories of Galina Petukhova and R Daniel Camerini-Otero have achieved significant technical advances in determining the genome-wide sites of DNA double-strand breaks (DSBs) where the process of genetic exchange between chromatids during meiosis begins. Applying the new approaches to male meiosis in mice, their experimental results considerably increase our insights into the nature and regulation of these processes.

In a recent landmark paper, the Huntington's disease (HD) iPSC Consortium reports on the establishment and characterization of a panel of iPSC lines from HD patients, and more importantly, the successful modeling of HD in vitro. In the same issue of Cell Stem Cell, An et al. reports on the successful targeted gene correction of HD in human iPSCs. Both advances are exciting, provide new resources for current and future HD research, and uncover new challenges to better understand and, most importantly, treat this devastating disease in the near future.

Salicylic acid (SA) is widely recognized as a key player in plant immunity. While several proteins have been previously identified as the direct targets of SA, SA-mediated plant defense signaling mechanisms remain unclear. The Nature paper from Xinnian Dong's group demonstrates that the NPR1 paralogues NPR3 and NPR4 directly bind SA, and this binding modulates their interaction with NPR1 and thereby degradation of this key positive regulator of SA-mediated defense, shedding important new insight into the mechanism(s) of SA-mediated, NPR1-dependent plant defense signal transduction.

Cap-dependent translation is initiated by the binding of eIF4E to the cap structure at the 5′ end of mRNAs. During hypoxic stress, global translation decreases because eIF4E is inactivated. In a recent article in Nature, Lee and colleagues show that residual hypoxic translation is maintained by a specialized isoform of eIF4E, which binds to target mRNAs in complex with a hypoxia-induced RNP.

The potentially life-threatening adverse reactions to Abavacir (ABC), a nucleoside analog reverse transcriptase inhibitor for the treatment of HIV infection, have been known for several years to be limited to individuals expressing the HLA-B^*57:01 gene. Why the ABC hypersensitivity syndrome is only seen in HLA-B^*57:01-expressing subjects and what the precise mechanisms underlying this intolerance are remain however controversial. A series of recent studies, particularly a study by Illing et al. recently published in Nature, now answer some of these questions and offer new opportunities to better understand autoimmune disorders and prevent adverse reactions to other drugs.