mutant. integration in an embryonic lethal mouse protein kinase II identified by transgene brain-specific Ca2+/calmodulin-dependent location of the gene for the beta subunit of Structure, expression, and chromosome

We sequenced the complete genome of the widely used C57L/J mouse inbred strain. With 40× average coverage, we compared the C57L/J sequence with that of the C57BL/6J and identified many known as well as novel private variants. This genome sequence adds another strain to the growing number of mouse inbred strains with complete genome sequences and is a valuable resource to the scientific community.

In bacterial cells, processing of double-stranded DNA breaks for repair by homologous recombination is dependent upon the recombination hotspot sequence Chi and is catalysed by either an AddAB- or RecBCD-type helicase-nuclease. Here, we report the crystal structure of AddAB bound to DNA. The structure allows identification of a putative Chi-recognition site in an inactivated helicase domain of ...

The capacity of the cell to produce, fold and degrade proteins relies on components of the proteostasis network. Multiple types of insults can impose a burden on this network, causing protein misfolding. Using thermal stress, a classic example of acute proteostatic stress, we demonstrate that ∼5-10% of the soluble cytosolic and nuclear proteome in human HEK293 cells is vulnerable to misfolding ...

The flagellar switch of Salmonella typhimurium and Escherichia coli is composed of three proteins, FliG, FliM, and FliN. The switch complex modulates the direction of flagellar motor rotation in response to information about the environment received through the chemotaxis signal transduction pathway. In particular, chemotaxis protein CheY is believed to bind to switch protein FliM, inducing clo...

We have explored the interchangeability of soluble and membrane proteins by attempting to render a helical membrane protein 'water soluble' through mutation of its lipid-exposed residues. Using an atomic resolution structure of bacteriorhodopsin (bR), two different strategies were developed to identify lipid-exposed residues for mutation. In the first strategy all residues in trimeric bR with s...

Recent studies have shown that Saccharomyces cerevisiae Msh2p and Msh6p form a complex that specifically binds to DNA containing base pair mismatches. In this study, we performed a genetic and biochemical analysis of the Msh2p-Msh6p complex by introducing point mutations in the ATP binding and putative helix-turn-helix domains of MSH2. The effects of these mutations were analyzed genetically by...

Underexpression of the transcriptional coactivator PGC-1 is causally linked to certain neurodegenerative disorders, including Huntington’s Disease (HD). HD pathoprogression is also associated with aberrant NMDAR activity, in particular an imbalance between synaptic versus extrasynaptic (NMDAR ) activity. Here we show that PGC-1 controls NMDAR EX activity in neurons and that its suppression cont...

dear editor analysis of the phenylalanine hydroxylase (pah mckusick 261600) gene in different populations has revealed more than 320 different mutations associated with phenylketonuria (pku). one of these mutations, ivs10nt546, results in severe pah deficiency due to defective mrna splicing. it accounts for about 40 percent of all mutant alleles in turkish and between 10 to 20 percent of all mu...