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An AAVgene targeting genomic map in human cells described by Deyle and colleagues reveals that homologous recombination occurs preferentially at sites where transcription and replication machineries converge. Cover by Erin Dewalt from map image by Ryan McVay/Photodisc/Thinkstock. PP 969–975
The fate of an mRNA is regulated by internal base modifications that generate the modified nucleotides N6-methyladenosine, 5-methylcytosine and inosine. Three new studies show that yeast and human mRNAs also contain pseudouridine residues and that pseudouridylation is induced in various stress states, hinting at a new pathway for post-transcriptional control of mRNA.
The human histone macroH2A.1.1 recruits activated PARP1 enzyme to chromatin through its poly(ADP-ribose)-binding macrodomain. New work shows that PARP1 and CBP can be displaced from chromatin in cancer cells that have lost macroH2A.1.1, thus leading to changes in histone H2B acetylation at cancer-relevant genes.
Emerging evidence from genome-wide analyses reveals that DNA methylation, an epigenetic modification associated with the repression of gene expression, can also promote transcriptional activation.
CAG-repeat expansion in the housekeeping gene ATXN7 causes the neurodegenerative disorder SCA7. Now ATXN7 protein is found to promote transcription and expression of miR-124, which in turn mediates cross-talk between lnc-SCA7 and ATXN7 transcripts.
Structural and biochemical analyses of full-length human BRCA2 reveal how it facilitates RAD51-mediated homologous recombination to repair DNA double-strand breaks.
A genome-wide screen of gene targeting by an adeno-associated virus vector in human cells reveals that target sites are preferentially located where transcription occurs in the opposite direction from DNA replication, suggesting that colliding polymerases promote homologous recombination.
Crystal structures of the extracellular domain of human nAChR, in its apo form and with antagonists methyllycaconitine or α-bungarotoxin bound, are presented. The structures provide insight into the channel-opening mechanism of nAChRs and their pharmacological properties.
Histone variant macroH2A1 represses gene expression in heterochromatin. New data show that it can also stimulate transcription by cooperating with PARP-1 to promote CBP-mediated H2B acetylation and that this regulatory function is lost in cancer cells.
The X-ray crystal structure of ScaDMT, a bacterial member of the solute carrier 11 transporter family, identifies conserved residues within the substrate-binding site that confer metal-ion selectivity.
U2AF is known to affect 3′-splice-site selection. Here, Fu and colleagues use genome-wide analysis of U2AF-RNA interactions to define U2AF's key roles in gene expression and regulated splicing in normal and disease states.
Crystal structures of MhsT, a bacterial member of the neurotransmitter/sodium symporter family, in an occluded, inward-facing state with bound sodium and substrate reveal conformational changes during the transport cycle that provide new insights into the mechanism of cytoplasmic sodium release.
An X-ray crystal structure of substrate-bound Neisseria PnuC, a bacterial member of the SWEET family of transporters, provides key insights into the translocation mechanism and potential evolution of these membrane proteins.