Sunday, April 15, 2012

Packaging reveals how genetic information gets modified

Our DNA holds the blueprint for our existence and consists of a long string of building blocks that represent coded information. It contains the blueprint for production of proteins in individual strings of code called genes. All genes combined is what we call the genome, and cells have found neat ways to package our genetic code. DNA is wound on beads to make it compact, and these wound up structures are stored in separate structures called chromosomes. In total, there are 23 chromosomes holding our entire genome, but because there is a paternal and maternal form of each chromosome, the total number of chromosomes reaches 46. They sometimes get mixed up and share genetic material with each other, a process that promotes genetic diversification and thus evolution. Cells require tight regulation to prevent damage, and two studies have revealed how chromosomes keep themselves properly packed.

As said, for each chromosome, there is a paternal and maternal version holding approximately the same genetic code. They are often entwined with each other and this connection is called a synapse. It allows them to swap genetic information, which can create slight differences in genes, and thus their function. This form of sharing is called crossing over and it is needed to pair up the chromosomes, but too many crossovers per pair can damage the structures because the DNA gets too mixed up. Scientists from the University of California in Davis have found three cellular tools that are involved with cutting the chromosomes in ways that ensure not too many crossovers occur. These enzymes were found in yeast, but human equivalents are known to exist.
Schematic showing two crossovers.
Copy number
Creating sperm of egg cells: A parent cell
replicates its DNA, and thus has 4 copies of
each chromosome. It is divided into four
daughter cells each having a single copy of
every chromosome.
By ensuring approximately the right amount of crossovers, the cell regulates processes that require pairing of chromosomes. This happens during meiosis, the process in which sperm or egg cells are created. Chromosomes are paired up so the paternal and maternal variant can be pulled apart by specialized structures, which means that only one copy will end up in the eventual sperm or egg cell. It is necessary for these cells to have just a single set of chromosomes, instead of the ordinary two copies per chromosome. When a sperm cell fertilizes an egg, they combine their genetic material, bringing the total number of copies per chromosome back to two in a fertilized egg. This would not work with ordinary cells containing two copies, as it would create fertilized eggs with four copies of each chromosome, which is not suitable for creating life.

There is another recently published study that also reveals a new regulatory element in the structure of chromosomes. Apparently, they pack themselves in a way that makes them look like a bunch of yarns. Though genes are thought of as long strings of code, that can only be regulated by elements lying in its vicinity, the 3D yarn structure provides new ways by which genetic elements can interact. Even though some DNA components, when looking at the string structure, are not close together, they can still influence each other's activity.
From right to left: DNA gets wound up tighter and tighter. The curled up structure shows how elements far from each other on the string can still interact with each other when wound up.
We already knew cells had ways to control genetic packaging, but this is the first time scientists have found enzymes that focus entirely on cutting chromosomes in order to regulate the number of crossovers. It reveals a new form of genetic regulation, just like the yarn structure mentioned above. According to the scientists, certain elements in the DNA can regulate activity of genes found to be in close physical range. It creates a cluster of genes that may not even be close together on the string of code, but still interact as if they were. These gene clusters can be turned on and off like switches by just one genetic element and their protein products are likely to be part of the same cellular process, which would provide a reason for their joint regulation.
Cells have tools to cut the DNA wound up in chromosomes, as metaphorically illustrated by the picture above.
Crossovers and chromosome structures have been studied intensively, revealing a strong link with cancer. When chromosomes share genetic information, genes on the 'border' of the crossover can be slightly modified, increasing or decreasing their activity. As a result, these genes can cause cancer, and many chromosomal changes have already been associated with specific forms of cancer. As for the regulation of crossovers, it is already known that the human forms of the chromosome cutters that were found are associated with cancer: mutated and dysfunctional variants increase the chance of developing tumours.

Regulation of chromosomal structures is important, as the consequence may be development of cancer. The aforementioned studies have revealed new ways by which cells regulate packages that hold the blueprint for our existence. The three chromosome cutting enzymes ensure an adequate amount of crossovers and thereby protect us from cancer. Additionally, by discovering the 3D yarn structure of chromosomes, we can study genetic interaction on a whole new level, and explain certain behaviour of genes, possibly also leading to new ways to prevent cancer. 

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