Volume 16 Issue 8, August 2009

The Mre11 protein has well-documented functions in the repair of DNA double-strand breaks via homologous recombination. Now, several new studies reveal that Mre11 also has a role in mammalian DNA double-strand break repair by nonhomologous end joining.

Male fruitflies upregulate transcription of nearly all genes on their single X chromosome to equalize expression with the two X chromosomes in females. A new study shows that the distribution of the histone acetylation mark associated with this upregulation is much broader than that of the MSL complex responsible for depositing this mark.

It is just as important to shut off a signaling pathway as it is to turn it on. A new study on the tandem Ras-associating (RA) and pleckstrin-homology (PH) domains of Grb10 and Grb14 provides important insight into a multicomponent assembly for downregulating insulin receptor signaling.

Bacterial antisense RNAs target translation initiation regions (TIRs) to compete with ribosome binding, thus repressing translation and—secondarily—causing degradation of the naked mRNA. A new study reports on an antisense RNA that directly accelerates mRNA decay by targeting a sequence deep within the coding region, far downstream of the TIR.

The MRN complex is known to have a role in the cellular response to DNA double-strand breaks in mammals, particularly in damage signaling, checkpoint responses and homologous recombination. Now MRN is found to function in nonhomologous end joining during mouse class switch recombination.

The MRN complex is known to have a role in the cellular response to DNA double-strand breaks in higher eukaryotes, particularly in damage signaling and checkpoint responses and homologous recombination. Now MRN is found to function in nonhomologous end joining in murine stem cells.

The MRN complex is known to play a role in the cellular response to DNA double-strand breaks in higher eukaryotes, particularly in damage signaling and checkpoint responses and homologous recombination. Now MRN is found to function in non-homologous end-joining in human and hamster cell lines.

Male Drosophila X chromosomes are highly transcribed to achieve dosage parity with females. This process is mediated by the MSL complex, though binding has been detected at only a subset of X chromosomal loci. MSL-dependent histone H4K16 acetylation is now found across the male X, suggesting widespread, but transient, MSL function.

Grb10 and Grb14 are adaptor proteins that inhibit insulin signaling through direct interactions with the insulin receptor kinase domain. Structural and functional studies now reveal that the tandem Ras-associating and pleckstrin-homology domains of these proteins are necessary for membrane recruitment and insulin receptor inhibition.

Bacterial small RNAs are generally thought to repress mRNAs at the level of translational initiation by binding in the 5′ untranslated region. Salmonella typhimurium MicC is now shown to target the ompD mRNA coding region, triggering decay without affecting translational initiation.

Nucleosomes can affect and be affected by processes targeting DNA. By comparing the in vitro positions of assembled nucleosomes on yeast DNA with in vivo positions, it is now concluded that intrinsic histone-DNA interactions are not the major determinant of nucleosome positioning in vivo.

Map belongs to a family of bacterial type III effectors that can regulate host cytoskeletal dynamics. Structural and biochemical data reveal that Map acts as a potent GEF for the GTPase Cdc42 and suggest how these effector molecules discriminate between target GTPases in their host.

The effects of translation factors on ribosome dynamics help drive protein synthesis. The ribosome was previously shown to fluctuate between two coordinated structural states during elongation. The effects of release and ribosome recycling factors on this conformational equilibrium are now examined.

CAG/CTG trinucleotide repeat expansion is linked to disorders such as Huntington's disease. These repeats tend to form stable hairpins that contribute to expansion. Removal of such DNA hairpins in human cell extracts is now found to occur via endonucleolytic incisions in an error-free manner followed by DNA synthesis.

The Plk1 kinase is a major regulator of mitosis that is often overexpressed in human cancers. Studies on phosphopeptide inhibitors specific to the polo-box domain of Plk1 reveal the determinants for specificity and may provide insight into the development of new therapeutics targeting protein-protein interactions.

Ubiquitin-associated (UBA) domains mediate diverse signaling events, and minimal UBA domains have been thought to harbor a range of polyubiquitin linkage specificities. Data now indicate that this may not be the case, but that specificity can arise through avid interactions with clusters of UBA domains.

Thioredoxins (Trxs) reduce disulfide bonds via a Michaelis-Menten mechanism. Upon substrate stretching at high forces, an S_N2 reaction can be used by bacterial Trxs. A third mechanism, single-electron transfer, is now revealed in Trxs of either bacterial or eukaryotic origin, and is correlated with the depth of the Trx substrate-binding groove.