Where and when do somatic mtDNA mutations occur?

It is generally assumed that somatic mtDNA mutations are originally created in the cells where these mutations are currently found. Accumulating data indicate, however, that cells with a particular mtDNA mutation tend to "cluster," that is, occur repeatedly within a given sample, but not in the others. Clusters likely are clonal, which implies that mtDNA mutations do not originate in the cells that currently carry them, but rather in those cells' progenitors, such as stem or satellite cells, or even earlier in the development.

RNA leaching of transcription factors disrupts transcription in myotonic dystrophy.

Myotonic dystrophy type 1 (DM1) is caused by a CUGn expansion (n approximately 50 to 5000) in the 3' untranslated region of the mRNA of the DM protein kinase gene. We show that mutant RNA binds and sequesters transcription factors (TFs), with up to 90% depletion of selected TFs from active chromatin. Diverse genes are consequently reduced in expression, including the ion transporter CIC-1, which has been implicated in myotonia.

Mechanism of Lac repressor switch-off: orientation of the Lac repressor DNA-binding domain is reversed upon inducer binding.

Lac repressor's DNA-binding domains contain helix-turn-helix motif which, though similar to those of phage lambda Cro protein, are oriented differently with respect to DNA: in the specific complexes with Lac operator, N termini of the repressor's subunits are facing inwards. We demonstrate that, in the presence of an inducer, the repressor's N termini cross-link to the operator's outermost nucleotides. We suggest that the inducer fixes the repressor's DNA-binding domains in the Cro-type configuration and thus garbles its recognition surface.

Nucleosomal structure at hyperacetylated loci probed in nuclei by DNA-histone crosslinking.

Chemically induced histone-DNA crosslinking in nuclei is used to monitor structural changes in chromosomal domains containing hyperacetylated histones. Core particles harbouring the crosslinks are immunofractionated with antibodies specific for acetylated histones. Crosslinking is revealed by gel separation of tryptic peptides from core histones that carry 32P-labelled residual nucleotide.