Thursday, October 30, 2008


At Telic Thoughts Bradford and some commenters recently exchanged polemics over chemical affinity of codons for their cognate amino acids. The alleged affinity was said to explain the origin of the genetic code. I had that in mind when I came upon a paper in Nature titled Structural insights into amino acid binding and gene control by a lysine riboswitch. It is authored by Alexander Serganov, Lili Huang and Dinshaw J. Patel. The paper notes that amino acid concentration within bacterial cells can be controlled by riboswitches. Of particular interest were lysine-specific riboswitches. The biosynthesis and transport of lysine can be directed by lysine-specific riboswitches.

How is amino acid recognition of riboswitches explained in molecular terms? The riboswitch has an unusual architecture. A five-helical junction connects three-helical and two-helical bundles. Lysine is recognized "through shape-complementarity within the elongated binding pocket and through several direct and K+-mediated hydrogen bonds to its charged ends."1 The authors wrote that:

Our structural and biochemical studies indicate preformation of the riboswitch scaffold and identify conformational changes associated with the formation of a stable lysine-bound state, which prevents alternative folding of the riboswitch and facilitates formation of downstream regulatory elements.2

1. Structural insights into amino acid binding and gene control by a lysine riboswitch by Alexander Serganov, Lili Huang and Dinshaw J. Patel; Nature 455, 1263-1267 (30 October 2008)

2. Ibid


Saturday, October 25, 2008

A Not So Common Event Connected with the Common Cold

Cold virus found to manipulate genes is a Biology News Net article which states the following:

For the first time, researchers have shown that HRV hijacks many of your genes and causes an overblown immune response that ends up with your nose being overblown.

The research, published in the first issue for November of the American Thoracic Society's clinical research journal, the American Journal of Respiratory and Critical Care Medicine, is the first study to comprehensively review gene changes caused by HRV.

HRV is an acronym for human rhinovirus which causes a large percentage of colds. Significantly the same virus is also implicated in more serious conditions like asthma and chronic obstructive pulmonary disease. Also from the article:

The researchers recruited volunteers who were inoculated with either HRV or a sham inoculation and obtained cell scrapings from the nasal passages 8 and 48 hours after inoculation and assessed the genetic changes by microarray, also know as gene chip technology.

After 8 hours, there were virtually no differences between the control and the HRV-inoculated group, but by the 48-hour mark, more than 6500 genes has been significantly up- or down-regulated in the HRV subjects—many of the more highly up-regulated genes fell into two major categories: genes making antiviral proteins, including viperin; or genes making pro-inflammatory cytokines.

So HRV affects the regulation of more than 6500 genes. Whew! Targeted genes include those coding for antiviral proteins and pro-inflammatory cytokines. The study also produced evidence that silencing the viperin-producing gene adversely impacted affected cells. Viperin hinders viral replication.


Monday, October 06, 2008

Creation or evolution - do we have to choose?

Over at "More Than Words", I've begun blogging/reviewing my way through Dr. Denis Alexander's new book in favour of theistic evolution, "Creation or Evolution: Do we have to choose?"

David Anderson


Sunday, October 05, 2008

Stability Enables DNA Repair

Control of DNA polymerase stability by phosphorylation and ubiquitination during the cell cycle (EMBO reports 9, 10, 1027–1033 2008; doi:10.1038/embor.2008.148) by Ursula Wimmer, Elena Ferrari, Peter Hunziker and Ulrich Hübscher, indicates that a DNA repair enzyme, dubbed DNA polymerase (Pol) (Greek letter lamda), is stabilized during the cell cycle through phophorylation. It is speculated that this enables the enzyme to repair damaged DNA during and after a phase of the cell cycle known as S. From the abstract (Greek letter lamda substituting for the actual symbol):

DNA polymerase (Pol) (Greek letter lamda) is a DNA repair enzyme involved in base excision repair, non-homologous end joining and translesion synthesis. Recently, we identified Pol as an interaction partner of cyclin-dependent kinase 2 (CDK2) that is central to the cell cycle G1/S transition and S-phase progression. This interaction leads to in vitro phosphorylation of Pol (Greek letter lamda), and its in vivo phosphorylation pattern during cell cycle progression mimics the modulation of CDK2/cyclin A. Here, we identify several phosphorylation sites of Pol (Greek letter lamda). Experiments with phosphorylation-defective mutants suggest that phosphorylation of Thr 553 is important for maintaining Pol (Greek letter lamda) stability, as it is targeted to the proteasomal degradation pathway through ubiquitination unless this residue is phosphorylated. In particular, Pol (Greek letter lamda) is stabilized during cell cycle progression in the late S and G2 phases. This most likely allows Pol (Greek letter lamda) to correctly conduct repair of damaged DNA during and after S phase.