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DNA and RNA polymerases active on bacterial and human genomes in the crowded environment of a cell are modeled as beads spaced along a string. Aggregation of the large polymerizing complexes increases the entropy of the system through an increase in entropy of the many small crowding molecules; this occurs despite the entropic costs of looping the intervening DNA. Results of a quantitative cost/benefit analysis are consistent with observations that active polymerases cluster into replication and transcription "factories" in both pro- and eukaryotes. We conclude that the second law of thermodynamics acts through nonspecific entropic forces between engaged polymerases to drive the self-organization of genomes into loops containing several thousands (and sometimes millions) of basepairs.

Original publication




Journal article


Biophys J

Publication Date





3712 - 3721


Computer Simulation, DNA, DNA-Directed DNA Polymerase, DNA-Directed RNA Polymerases, Entropy, Genome, Models, Chemical, Models, Molecular, Nucleic Acid Conformation