Sunday, August 17, 2008

Supercoiling and DNA

What's notty about DNA? discusses an important property of DNA i.e. supercoiling. The twisting of the DNA helix around what could be envisioned as a central line can be described by the mathematical formula: Lk = Tw+Wr where the sum of the twist about the central line and the writhe (the amount of resistance to straightening the curve) equals the number of times one of the strands winds around the other one.

The linked article contains these quotes identifying supercoiling properties which enable the described functions.

Supercoiling is a very smart form of compact storage that allows for easy manipulation.

Supercoiling allows for easy manipulation and so easy access to the information coded in the DNA. When a cell is copying a DNA strand it will uncoil a strand, copy it and then recoil it.

The compact storage of genetic information and facilitated access to that information can be attributed to topological properties of DNA. We see design features that enhance the function of cells. But let's look at the other side of this coin namely, design constraints

Behavior of Supercoiled DNA, Biophys J, April 1998, p. 2016-2028, Vol. 74, No. 4 and authored by T. R. Strick, J.-F. Allemand, D. Bensimon, and V. Croquette, states this:

Vinograd first understood in 1965 (Vinograd et al., 1965) that the double-helical nature of DNA allows it to be overwound and underwound from its natural state. Today we know that DNA is topologically polymorphic. The overwound or underwound double helix can assume exotic forms known as plectonemes (like the braided structures of a tangled telephone cord) or solenoids (similar to the winding of a magnetic coil) (Marko and Siggia, 1995). These tertiary structures have an important effect on the molecule's secondary structure and eventually its function. For example, supercoiling-induced destabilization of certain DNA sequences can allow the extrusion of cruciforms (Palacek, 1991) or even the transciptional activation of eukaryotic promoters (Dunaway and Ostrander, 1993).

So supercoiling also can lead to overwinding, causing destabilization of function. Another quote:

DNA replication poses a similar but topologically enhanced problem. Once replication is completed, the newly synthesized molecule must be disentangled from its parent. The replication of circular DNA molecules gives rise to two linked circular molecules, but the replication of whole chromosomes leaves the cell with highly entangled chromatids. If the cell does not disentangle the freshly replicated pairs of sister chromatids, they will fragment under the pull of the mitotic spindle. Disentanglement is achieved thanks to topoisomerases (Jannink et al., 1996). Topoisomerases are the cell's tools for managing the topologies of their genomes (Wang, 1996). Type I topoisomerases act by transiently breaking one of the strands of duplex DNA, allowing the intact strand to pass through and thereby changing the number of times the two strands wrap. Type II topoisomerases transiently break both strands of duplex DNA, allowing another segment of duplex DNA to pass through. Type II topoisomerases thus have an unknotting activity, which is required to disentangle linked circles or replicated chromosomes.

The DNA replication process brings about molecular entaglements. Disentanglement is needed to retain DNA function. Enzymes known as topoisomerases enable the disentangling. The entanglement problem is inherent to DNA topology. A design enhancement is also a design flaw whether the designer is viewed as a force of nature, culled by selection, or a more directing cause. This type of flaw calls for a remedy built into the design itself. That's what we witness. The remedy (topoisomerases) are coded for by genes found in DNA. This is a logical indicator of a front loaded option. If not front loaded how would the entanglement dilemna be resolved. Gradual evolution is not helpful when an affliction is immediate and universal. Neither is extinction.

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