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Chemical Eye on Motherly Love
by Preston MacDougall

 

May 17, 2006
Wednesday


Mothers galore awaited a visit, flowers, a telephone call, or maybe even a public radio commentary from their children this weekend. You should know that she loves you, right down to the molecular level.

For starters, she put a snug little cap on the end of your lagging strand to prevent you from catching your death of oldness too soon. She did this before you were born, before you were even conceived. She did this even before you were a twinkle in your father's eye. Let me explain.

jpg Motherly Love

Credit: morguefile.com

As you probably know, all forms of life that we know about use DNA to encode the instructions for the molecular tool-kits that are responsible for both our innate outward appearance and inward personal chemistry. For humans, DNA comes in pairs. Twinned right-handed helices to be exact.

Well, not exactly. Both helices are right-handed, alright, but they are chemically oriented in opposite directions. Imagine a two-lane highway that twists continuously like a corkscrew roller-coaster.

While cars on a highway can be inbound, outbound, or stopped in traffic, the chemical terminology for directions along DNA strands is 5' to 3', and vice versa. These directions refer to the numerical nicknames that chemists have assigned to the five carbon atoms of a ribose molecule.

It may help if you think of the ribose units as cars stuck in a traffic jam, with a phosphate buffer zone between them. In this analogy, the rear bumper is carbon 5, the front bumper is carbon 3, and the nitrogenous base that it contributes to the code is jutting out the driver-side window. Please note that ribose units are styled after British cars, and they drive on the left.

Another difference is that the strands have complementary, as opposed to identical codes. This is what makes them stick together, sort of like Velcro. But instead of hooks catching loops, in DNA the A's stick to the T's and the C's stick to the G's. While both strands are copied whenever a cell divides, only the instructions of one strand are read during normal cell operation.

Cell division is a miraculous event. Among other feats, all 23 pairs of chromosomes, which are themselves double-stranded DNA molecules, must be copied without error. The shortest, number 21, of which people with Down's syndrome have a triplet instead of a pair, has 50 million letters in its genetic code. This means it also has 50 million ribose units, going each way.

Even without the latest spike in the price of gas, it would be foolish for an airborne traffic reporter to cruise 25 miles into town, reporting on inbound traffic, then turn around and cruise 25 miles out of town to report on outbound traffic, on the same highway. Likewise, during cell division, mother nature's little helpers, enzymes called DNA polymerases, copy both strands at the same time.

The so-called leading strand is easy. It is done smoothly since this is where synthesis is done "with the flow of traffic", or 5' to 3'. The other strand, the lagging strand that I referred to earlier, is tricky because the enzymes are built to only work in the 5' to 3' direction. This strand's new mate is made in a piecemeal fashion, but always putting one ribose "car" in front of the last. When the machinery finishes one stretch, it backtracks and starts again on a new piece.

James Watson, of Watson and Crick fame, was the first to realize that this replication scenario runs into a problem at the end of the lagging strand, where there isn't enough room to back up the machinery. As a result, when a cell divides, the leading strand is replicated fully, but the lagging strand loses from 50 to 100 letters in its code, always at the very end.

The ends of chromosomes are called telomeres. They are long when we are conceived, and they get shorter as we develop normally. It is thought that the ageing process is closely tied to the intricacies of telomere chemistry. Research continues apace, against the clock you might say.

One of the most interesting discoveries concerning telomeres was guided by pure logic. Why, after thousands of generations of human ancestry, are we still born with long telomeres?

The answer is that there is another enzyme capable of extending the telomeres back to their original length, or "capping" the ends. This enzyme has since been isolated, and it is called telomerase. It is active in sex cells, eggs for her and sperm for him, and some stem cells, but not in normal adult cells that show signs of age.

So your mother not only gave you your start in life, she also took molecular steps to minimize the odds of an early finish.

 

 

Preston MacDougall is a chemistry professor at Middle Tennessee State University. His "Chemical Eye" commentaries are featured in the Arts and Public Affairs portion of the Nashville/Murfreesboro NPR station WMOT (www.wmot.org).




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