Research articles

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Covalent histone modifications have been linked to many DNA processes. The repertoire of modifications is still growing, and histone H3K64 trimethylation is now shown to be localized to pericentric chromatin and its levels dynamically altered during developmental reprogramming in both embryos and primordial germ cells.

Transient receptor potential channels are involved in sensory perception, and TRPV1 is a sensor of burning pain signals and can be modulated by acidic pH, capsaicin and heat. Substituted cysteine accessibility is used to probe state-dependent structural arrangements of the presumed pore-lining S6 helix, revealing two constrictions that participate in gating activity of the channel pore.

Hedgehog (Hh) proteins are involved in multiple developmental processes. Hedgehog-interacting proteins (Hhips) bind and inhibit vertebrate Hh proteins. A structure of HHIP in complex with human SHH now shows a distinct binding site from previous ligand structures, with the pseudocatalytic site having a key role in binding.

Hedgehog (Hh) signaling molecules are involved in multiple developmental processes. Hedgehog-interacting protein (Hhip) binds and inhibits vertebrate Hh proteins. Structures of HHIP in complex with SHH and DHH now show a distinct binding site from previous ligand structures, with metal-binding sites having a role in interaction.

Exogenously applied small RNAs have previously been shown to inhibit transcriptional levels when targeted to promoters. They are now shown to alter the ratio of alternative splice forms. The features of splice form alteration are reminiscent of transcriptional gene silencing by siRNAs.

Clostridium botulinum neurotoxins (BoNTs) cleave proteins involved in neurotransmitter release, with different serotypes showing distinct cleavage specificity. The structure of BoNT F with peptide inhibitors based on the VAMP substrate give insight into residues crucial for substrate binding and catalysis.

The lamprey adaptive immune system is evolutionarily distinct from ours and based on recognition by leucine-rich repeat proteins rather than antibodies. The crystal structure of a lamprey variable lymphocyte receptor in complex with a protein antigen now gives insight into how a distinct adaptive immune molecule recognizes a protein antigen.

AID is a DNA cytidine deaminase that participates in the generation of antibody diversity. AID's mutagenic activity is carefully controlled by transcriptional and post-translational mechanisms. Now the enzyme's intrinsic catalytic activity is found to have been kept low during evolution, and in vitro–selected AID upmutants can cause genetic instability.