Monday, December 12, 2011

Transcription and Translation

This video provides a brief overview about transcription and translation. It explains the difference between the two. This has always been a hard concept for me to grasp because I always used to get the two processes confused. This video is clear and explains these two processes in great detail. Included in the powerpoint that he goes over, are some fun animated videos that help explain these two processes.

Sunday, December 11, 2011

Identical Twins: Not as Identical as You Think

This article talks about how identical twins show differences in their gene expressions. In many aspects, identical twins seem, well, identical! However, there are dissimilarities and it is unclear how they have come about. A new report suggests that epigenetic differences, differences in how the genome is expressed, could be responsible. Mario F. Fraga, of the Spanish National Cancer Center, studied 160 identical twins, ranging in all different ages. Two external factors through the entire genome were analyzed for each set of twins. Both DNA methylation and histone acetylation govern gene expression and can magnify or reduce the effects of certain genes. The team's research showed that twins tended to be indistinguishable in their gene expression, earlier in life. As the twins got older, more differences in gene expression became evident. Also, twins who had spent more time apart and had more varying medical histories showed the greatest epigenetic differences.


This is a picture of methylation patterns of three-year-old twins (left) and 50-year-old twins (right). The differences have been highlighted in red.


Environmental factors, physical activity levels, and diet can influence epigenetic patterns and may help in understanding how the same genotype can be translated in different ways. Scientists suggest that specific mechanisms that cause this so-called epigenetic drift in identical twins should be studied in the future.

Tetrahymena Telomerase

This article talks about the structural basis for Tetrahymena telomerase processivity factor Teb1 to single-stranded telomeric-repeat DNA. Telomerase is an enzyme that adds nucleotides to telomeres, especially in cancer cells. When DNA is synthesized, it loses a part of it's telomere each time. These are protective compound structures located at the ends of chromosomes. Telomerase duplicates its own internal RNA template to synthesize telomeric DNA repeats. Unlike other polymerases, telomerase can retain its single-stranded product through many rounds of template dissociation and repositioning to accomplish repeat addition processivity (RAP). Tetrahymena telomerase holoenzyme RAP is dependent on a subunit, Teb1, with independent DNA-binding activity. Sequence homology and domain modeling tell us that Teb1 is a paralog of RPA70C, the largest subunit of the single-stranded DNA-binding factor replication protein (RPA), but unlike RPA, Teb1 binds DNA with high specificity for telomeric repeats.


This is an animated picture of a Tetrahymena Telomerase molecule.


To begin to understand the structural basis and significance of telomeric-repeat DNA recognition by Teb1, researchers had to solve crystal structures of three proposed Teb1 DNA-binding domains and defined amino acids of each domain that had contributed to DNA interaction. Their studies indicate that two central Teb1 DNA-binding oligonucleotide/oligosaccharide-binding-fold domains, Teb1A and Teb1B, achieve high affinity and selectivity of telomeric-repeat recognition by principles similar to the telomere end-capping protein POT1 (protection of telomeres 1). An additional C-terminal Teb1 oligonucleotide/oligosaccharide-binding-fold domain, Teb1C, has similar characteristics as the RPA70 C-terminal domain including a presumed direct DNA-binding surface that is very important for high-RAP activity of reconstituted holoenzyme (which is a biochemically active compound formed by the combination of an enzyme with a coenzyme). The Teb1C zinc ribbon motif does not contribute to DNA binding but is nonetheless required for high-RAP activity, perhaps contributing to Teb1 physical association with the remainder of the holoenzyme. This research team's results suggest the biological model that high-affinity DNA binding by Teb1AB raises holoenzymes to telomeres and subsequent Teb1C-DNA association traps the product in a sliding-clamp-like manner that does not require high-affinity DNA binding in order to achieve high stability of enzyme-product association.

Thursday, December 1, 2011

Leading vs. Lagging Strands

This is an excellent video to watch if you are having trouble understanding leading and lagging strands. It gives a basic explanation of leading vs. lagging strand replication during DNA synthesis. He goes through all of the basic steps from template orientation to the rNA primer to which enzymes were used where. He also explains Okazaki fragments which were a hard concept for me to grasp. Overall, this video was very helpful in clarifying each of the basic steps in DNA synthesis.

My, What Long Telomeres You Have

This article talks about telomeres and what they say about you. For example, smokers and couch potatoes are common offenders of damaging their chromosomes. Two groups of well known researchers have started companies solely to come up with a test that can measure the length of someone's telomeres. Telomeres are caps on the ends of chromosomes meant to protect. A good analogy is to think of them as plastic tips on the ends of shoelaces that keep the laces from fraying.


These are chromosomes capped with telomeres.
The telomeres appear bright, on the ends.


Whenever chromosomes—the store­houses of our genes—are replicated for cell division, their telomeres shorten. Many scientists have been led to believe that this shortening has led  to view telomere length as a marker of biological aging. Similar to a “molecular” clock telling the cell’s life span, as well as an indicator of overall health. Studies have compared telomere length of white blood cells among groups of volunteers; they have found that there were many distinct correlations between telomere length and lifestyle. Those who were exercising regularly had longer telomeres than those who did not. Folks who perceived themselves as the most stressed had shorter telomeres than those who saw themselves as the least. Certain diseases also seemed to correlate with shorter telomeres, including cardiovascular, obesity and Alzheimer’s.
In the future, telomere research can tell us more about our health. Knowing whether our telomeres are of normal length or not for a given chronological age will tell us about the status of our health status and our physiological "age". Telomere length is probably the best single measure of our integrated genetics, previous lifestyle and environmental exposures.
Although research has gotten very far, telomere experts still haven’t defined what they consider to be a norm and what they consider to be abnormal, either long or short. Regardless, the data, would be  sufficient to help people make personal lifestyle decisions regarding diet, exercise, and stress.