Brownian Chain Evolution: A Propulsion Mechanism?


Donald Drew, Rensselaer Polytechnic Institute, Troy, New York


E. coli is a simple organism that is easy to study, and has evolved clever ways to accomplish its several tasks.  One of these tasks involves the control of starting DNA replication.  Another is the propulsion system for migration of the replicated DNA into opposite ends of the cell in preparation for cell division.  The modeling effort examines a mechanism involving a single protein which may have a role in both processes.


The DNA of E. coli forms a loop.  When it divides, E. coli replicates its DNA starting at a location called oriC.  The replication proceeds both ways along the loop, meeting at a location called ter. E. coli has evolved a regulation mechanism so that re-initiation cannot occur too soon during replication.  This mechanism involves the binding of a protein called SeqA to newly replicated sites on the DNA marked by the sequence GATC.  SeqA is also capable of binding to itself.  Researchers have identified clumps of SeqA near the origin sites of replicating DNA, which split and migrate toward the opposite sides of the cell (see Figure 1).  Biologists have sought a "propulsion molecule" in E. coli, but have been unsuccessful.  We shall derive a model for, and study a mechanism by which the binding of SeqA to the newly-replicated DNA and to itself could result in loops of DNA, which when released by the SeqA bundles, could straighten to propel the remaining SeqA and DNA apart.




Figure 1.  SeqA binding DNA, then itself causes loops in the DNA.



The proposed mechanism is as follows: As the newly formed DNA emerges from the DNA polymerase family, it is bound by SeqA at GATC sites, and the clumping property of SeqA cause the DNA to form loops.  These loops have a high degree of "order", which can be thought of as an energy stored as bending.  As the SeqA molecules become unbound from the GATC sites, the loops can straighten.  If the straightening is unsymmetrical, the different DNA strands can be pushed in different directions (see Figure 2).





Figure 2.  Asymmetry in SeqA release of DNA causes migration of SeqA clusters and the replication factories.







[1] Sota Hiraga, Chiyome Ichinose, Toshinari Onogi, Hironori Niki and Mitsuyoshi Yamazoe, Bidirectional migration of SeqA-bound hemimethylated DNA clusters and pairing of oriC copies in Escherichia coli, Genes Cells, 5 (2000), 327-41.


[2] Toshinari Onogi, Hironori Niki, Mitsuyoshi Yamazoe and Sota Hiraga, The assembly and migration of SeqAGfp fusion in living cells of Escherichia coli, Molecular Microbiology, 31 (1999), 17751782.