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.

AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification

Abstract: After gene rearrangement, immunoglobulin variable genes are diversified by somatic hypermutation or gene conversion, whereas the constant region is altered by class-switch recombination. All three processes depend on activation-induced cytidine deaminase (AID)1,2,3,4,5,6,7, a B-cell-specific protein that has been proposed (because of sequence homology1) to function by RNA editing. But indications that the three gene diversification processes might be initiated by a common type of DNA lesion8,9,10,11, together with the proposal that there is a first phase of hypermutation that targets dC/dG12, suggested to us that AID may function directly at dC/dG pairs. Here we show that expression of AID in Escherichia coli gives a mutator phenotype that yields nucleotide transitions at dC/dG in a context-dependent manner. Mutation triggered by AID is enhanced by a deficiency of uracil-DNA glycosylase, which indicates that AID functions by deaminating dC residues in DNA. We propose that diversification of functional immunoglobulin genes is triggered by AID-mediated deamination of dC residues in the immunoglobulin locus with the outcome—that is, hypermutation phases 1 and 2, gene conversion or switch recombination—dependent on the way in which the initiating dU/dG lesion is resolved.

Tau pathology and neurodegeneration

Abstract: The pathway leading from soluble and monomeric to hyperphosphorylated, insoluble and filamentous tau protein is at the centre of many human neurodegenerative diseases, collectively referred to as tauopathies. Dominantly inherited mutations in MAPT, the gene that encodes tau, cause forms of frontotemporal dementia and parkinsonism, proving that dysfunction of tau is sufficient to cause neurodegeneration and dementia. However, most cases of tauopathy are not inherited in a dominant manner. The first tau aggregates form in a few nerve cells in discrete brain areas. These become self propagating and spread to distant brain regions in a prion-like manner. The prevention of tau aggregation and propagation is the focus of attempts to develop mechanism-based treatments for tauopathies.