Phage Mu transposition immunity: protein pattern formation along DNA by a diffusion-ratchet mechanism.
DNA transposons integrate into host chromosomes with limited target sequence specificity. Without mechanisms to avoid insertion into themselves, transposons risk self-destruction. Phage Mu avoids this problem by transposition immunity, involving MuA-transposase and MuB ATP-dependent DNA-binding protein. MuB-bound DNA acts as an efficient transposition target, but MuA clusters bound to Mu DNA ends activate the MuB-ATPase and dissociate MuB from their neighborhood before target site commitment, making the regions near Mu ends a poor target. This MuA-cluster-MuB interaction requires formation of DNA loops between the MuA- and the MuB-bound DNA sites. At early times, MuB clusters are disassembled via loops with smaller average size, and at later times, MuA clusters find distantly located MuB clusters by forming loops with larger average sizes. We demonstrate that iterative loop formation/disruption cycles with intervening diffusional steps result in larger DNA loops, leading to preferential insertion of the transposon at sites distant from the transposon ends.
Han
Yong-Woon
YW
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
Mizuuchi
Kiyoshi
K
D010583:Bacteriophage mu / Q000201:enzymology / Q000378:metabolism*; D004251:DNA Transposable Elements / Q000235:genetics*; D004279:DNA, Viral / Q000737:chemistry / Q000378:metabolism*; D004058:Diffusion; D005456:Fluorescent Dyes / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D009038:Motion; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D019895:Transposases / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*
D004251:DNA Transposable Elements; D004279:DNA, Viral; D005456:Fluorescent Dyes; D014764:Viral Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D019895:Transposases