Bullied no more: when and how DNA shoves proteins around.

The predominant protein-centric perspective in protein-DNA-binding studies assumes that the protein drives the interaction. Research focuses on protein structural motifs, electrostatic surfaces and contact potentials, while DNA is often ignored as a passive polymer to be manipulated. Recent studies of DNA topology, the supercoiling, knotting, and linking of the helices, have shown that DNA has the capability to be an active participant in its transactions. DNA topology-induced structural and geometric changes can drive, or at least strongly influence, the interactions between protein and DNA. Deformations of the B-form structure arise from both the considerable elastic energy arising from supercoiling and from the electrostatic energy. Here, we discuss how these energies are harnessed for topology-driven, sequence-specific deformations that can allow DNA to direct its own metabolism.

Hin-mediated DNA knotting and recombining promote replicon dysfunction and mutation.

BACKGROUND: The genetic code imposes a dilemma for cells. The DNA must be long enough to encode for the complexity of an organism, yet thin and flexible enough to fit within the cell. The combination of these properties greatly favors DNA collisions, which can knot and drive recombination of the DNA. Despite the well-accepted propensity of cellular DNA to collide and react with itself, it has not been established what the physiological consequences are. RESULTS: Here we analyze the effects of recombined and knotted plasmids in E. coli using the Hin site-specific recombination system. We show that Hin-mediated DNA knotting and recombination (i) promote replicon loss by blocking DNA replication; (ii) block gene transcription; and (iii) cause genetic rearrangements at a rate three to four orders of magnitude higher than the rate for an unknotted, unrecombined plasmid. CONCLUSION: These results show that DNA reactivity leading to recombined and knotted DNA is potentially toxic and may help drive genetic evolution.

Conservation of writhe helicity under anti-parallel reconnection.

Reconnection is a fundamental event in many areas of science, from the interaction of vortices in classical and quantum fluids, and magnetic flux tubes in magnetohydrodynamics and plasma physics, to the recombination in polymer physics and DNA biology. By using fundamental results in topological fluid mechanics, the helicity of a flux tube can be calculated in terms of writhe and twist contributions. Here we show that the writhe is conserved under anti-parallel reconnection. Hence, for a pair of interacting flux tubes of equal flux, if the twist of the reconnected tube is the sum of the original twists of the interacting tubes, then helicity is conserved during reconnection. Thus, any deviation from helicity conservation is entirely due to the intrinsic twist inserted or deleted locally at the reconnection site. This result has important implications for helicity and energy considerations in various physical contexts.

Quantitative comparison and analysis of brain image registration using frequency-adaptive wavelet shrinkage.

In the field of template-based medical image analysis, image registration and normalization are frequently used to evaluate and interpret data in a standard template or reference atlas space. Despite the large number of image-registration (warping) techniques developed recently in the literature, only a few studies have been undertaken to numerically characterize and compare various alignment methods. In this paper, we introduce a new approach for analyzing image registration based on a selective-wavelet reconstruction technique using a frequency-adaptive wavelet shrinkage. We study four polynomial-based and two higher complexity nonaffine warping methods applied to groups of stereotaxic human brain structural (magnetic resonance imaging) and functional (positron emission tomography) data. Depending upon the aim of the image registration, we present several warp classification schemes. Our method uses a concise representation of the native and resliced (pre- and post-warp) data in compressed wavelet space to assess quality of registration. This technique is computationally inexpensive and utilizes the image compression, image enhancement, and denoising characteristics of the wavelet-based function representation, as well as the optimality properties of frequency-dependent wavelet shrinkage.