Laboratory of Molecular Biology

About: Laboratory of Molecular Biology is a facility organization based out in Cambridge, Cambridgeshire, United Kingdom. It is known for research contribution in the topics: Gene & RNA. The organization has 19395 authors who have published 24236 publications receiving 2101480 citations.

Evidence for evolutionary conservation of sex-determining genes

Abstract: Most metazoans occur as two sexes. Surprisingly, molecular analyses have hitherto indicated that sex-determining mechanisms differ completely between phyla. Here we present evidence to the contrary. We have isolated the male sexual regulatory gene mab-3 from the nematode Caenorhabditis elegans and found that it is related to the Drosophila melanogaster sexual regulatory gene doublesex (dsx)2. Both genes encode proteins with a DNA-binding motif that we have named the 'DM domain'. Both genes control sex-specific neuroblast differentiation and yolk protein gene transcription; dsx controls other sexually dimorphic features as well. The form of DSX that is found in males can direct male-specific neuroblast differentiation in C. elegans. This structural and functional similarity between phyla suggests a common evolutionary origin of at least some aspects of sexual regulation. We have identified a human gene, DMT1, that encodes a protein with a DM domain and find that DMT1 is expressed only in testis. DMT1 maps to the distal short arm of chromosome 9, a location implicated in human XY sex reversal. Proteins with DM domains may therefore also regulate sexual development in mammals.

Conformation of the Bax C‐terminus regulates subcellular location and cell death

Abstract: Bax, a pro-apoptotic member of the Bcl-2 family, translocates from the cytosol to the mitochondria during programmed cell death. We report here that both gain-of-function and loss-of-function mutations can be achieved by altering a single amino acid in the Bax hydrophobic C-terminus. The properly mutated C-terminus of Bax can target a non-relevant protein to the mitochondria, showing that specific conformations of this domain alone allow mitochondrial docking. These data along with N-terminus epitope exposure experiments suggest that the C- and the N-termini interact and that upon triggering of apoptosis, Bax changes conformation, exposing these two domains to insert into the mitochondria and regulate the cell death machinery.

Fusion between immunoglobulin-secreting and nonsecreting myeloma cell lines.

Abstract: The defects in two nonsecreting variant clones of the mouse plasmacytoma MOPC 21 (P3) were studied by tissue culture methods. The variants (NSI and NSIII) do not synthesize detectable heavy chains. NSI synthesizes, but does not secrete, light chains and NSIII does not synthesize light chain. A screening procedure was used allowing the detection of revertant cells secreting immunoglobulin. The method is based on a hemolytic plaque assay using anti-immunoglobulin-coated red cells. No revertants were detected among 2 x 10(7) cells. Both variant lines were fused to another myeloma line (PI) which secretes a complete immunoglobulin and excess light chains. Analysis of the products by isoelectric focusing showed that in the hybrids there was no reactivation of synthesis of the nonexpressed chains. The defects leading to loss of synthesis cannot therefore be complemented in the hybrid lines. The secretion of light chain in NSI, on the other hand, could be complemented in the hybrid but the light chain was only secreted as part of a new immunoglobulin hybrid molecule.