Volume 6 Issue 10, October 2010

Biological messiness relates to infidelity, heterogeneity, stochastic noise and variation—both genetic and phenotypic—at all levels, from single proteins to organisms. Messiness comes from the complexity and evolutionary history of biological systems and from the high cost of accuracy. For better or for worse, messiness is inherent to biology. It also provides the raw material for physiological and evolutionary adaptations to new challenges.

A polymer scientist explores and exploits the heterogeneity of natural biopolymers.

Iron-sulfur (Fe-S) clusters are among nature's simplest and most versatile agents of electron transfer. Remarkably, their biological assembly involves an obligatory electron transfer event. It is now revealed that parallel but distinct electron transfer pathways are separately required for compartment-specific Fe-S protein maturation.

Mutually exclusive post-translational modifications of flap endonuclease 1 (FEN1) regulate its binding to proliferating cell nuclear antigen (PCNA) and govern its various modes of DNA interaction during DNA replication and repair.

Spider dragline silk is an incredibly tough elastomer, but it is also very elastic. Recent work has demonstrated how the mechanical properties of spider silk and other natural elastomers can be mimicked to produce artificial protein-based fibers with great potential for industrial applications.

Enzymatic conversion of adenosine to inosine is an RNA editing mechanism for post-transcriptional diversification of mRNA. A new chemical tagging–reverse transcription method leads to the identification of new A-to-I RNA editing sites in the human genome.

Secretion of strigolactone from plant roots mediates mutualistic fungal interactions but also facilitates parasitic plant invasion. A screen in Arabidopsis thaliana has identified compounds that perturb strigolactone levels and link this hormone to light signaling pathways in host plants.

The multiple lysines that can link ubiquitin chains have created challenges in studying these important biopolymers. The ribosomal incorporation of a protected lysine analog now allows the specific construction of native K6- and K29-linked diubiquitin chains, enabling structural analysis and deubiquitinase profiling.

Iron-sulfur clusters are essential components of many proteins and are assembled in a hierarchical pathway. Tah18 is a diflavin reductase that transfers electrons to the [2Fe-2S] cluster of Dre2 in an early step of iron-sulfur cluster biogenesis in the cytoplasm of eukaryotes.

Structure-specific flap endonuclease 1 (FEN1) is known to interact with multiple nuclear proteins involved in DNA metabolism. Arginine methylation in FEN1 blocks phosphorylation of a nearby serine and enhances FEN1 binding to PCNA, which serves to channel FEN1 toward DNA replication and repair pathways.

Polymerase exclusion of ribonucleotides during DNA replication is imperfect. New data indicate that DNA polymerase ϵ incorporates into DNA ribonucleotides that are repaired by an RNase H2–dependent process and that defective repair results in replicative stress and genome instability.

Chemical biologists are asking and answering molecular level questions that expand our awareness and understanding of structural and functional variation. In this issue, we feature profiles, opinions and guides that highlight the complexity of the natural world.