The lac repressor displays facilitated diffusion in living cells.

Science

Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Published: June 2012

AI Article Synopsis

  • Transcription factors (TFs) are proteins that control gene expression by binding to specific sites on chromosomes, using a combination of 1D sliding on DNA and 3D diffusion in the cytoplasm to locate these sites quickly.
  • A new single-molecule assay was developed to study the sliding behavior of the lac repressor in living bacteria, revealing that it can slide approximately 45 base pairs of DNA and may encounter obstacles from other DNA-bound proteins.
  • The study found that the lac repressor often slides over its target site multiple times before binding, indicating a balance between searching quickly through nonspecific regions and making fast, effective connections at specific sequences.

Article Abstract

Transcription factors (TFs) are proteins that regulate the expression of genes by binding sequence-specific sites on the chromosome. It has been proposed that to find these sites fast and accurately, TFs combine one-dimensional (1D) sliding on DNA with 3D diffusion in the cytoplasm. This facilitated diffusion mechanism has been demonstrated in vitro, but it has not been shown experimentally to be exploited in living cells. We have developed a single-molecule assay that allows us to investigate the sliding process in living bacteria. Here we show that the lac repressor slides 45 ± 10 base pairs on chromosomal DNA and that sliding can be obstructed by other DNA-bound proteins near the operator. Furthermore, the repressor frequently (>90%) slides over its natural lacO(1) operator several times before binding. This suggests a trade-off between rapid search on nonspecific sequences and fast binding at the specific sequence.

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http://dx.doi.org/10.1126/science.1221648DOI Listing

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