Newswise —
"Is that truly feasible?" pondered scientist Benjamin Rowland. He recollects the telephonic exchange with his associate from England. "We noticed a dubious resemblance between two molecules in our cellular nucleus. They appeared to contain precisely identical components in one region, which may elucidate numerous cellular occurrences. Hence, naturally, we had to scrutinize it!"
X in biology textbooks
In our organism, cells undergo continuous division to generate new cells. During this process, a cell replicates its DNA and evenly partitions it between the two resultant cells. This task is easier said than done. Considering that our DNA is several meters in length and densely packed like strands of spaghetti within the minuscule nucleus of a cell, achieving fair distribution is quite a challenge.
Cells have a cunning mechanism to address this issue. They duplicate their DNA and condense it into compact bundles. During this process, the cells keep the two copies connected in the middle until they undergo division. When viewed under a microscope, this condensed bundle appears as an X shape (as depicted in images found in biology textbooks).
Exotic name
Right before cell division, the X-shaped bundle separates in the middle, and each arm of the X migrates towards opposite ends of the cell. If this process is disrupted, the resultant cells can end up with unequal amounts of DNA, which can lead to abnormalities. Cancer cells, for instance, frequently contain abnormal quantities of DNA.
"The structure of a chromosome is essentially two identical elongated DNA strands that are initially joined along their entire length," explains researcher Benjamin Rowland. A group of circular cohesin molecules bind the two strands together. "As the cell prepares to divide, the cohesin rings separate, causing the DNA arms to split apart. However, the rings located in the center of the DNA remain tightly bound together, thanks to a protein called shugoshin, also known as SGO1."
Locked rings
For over a century, biology textbooks have depicted chromosomes as having an X shape, yet the underlying mechanism has remained an enigma for quite some time. However, Rowland's PhD student Alberto García-Nieto has recently uncovered that shugoshin employs a molecular key that perfectly fits into a type of keyhole present in cohesin. This process results in the locking of the cohesin rings, and since shugoshin operates exclusively at the center of chromosomes, it is only there that the rings are locked, thereby giving chromosomes their characteristic X shape. Once the cell has aligned everything properly for division, it subsequently cuts the final rings using molecular scissors. This leads to the separation of DNA, allowing the cell to divide.
Universal mechanism
The researchers stumbled upon an unexpected similarity that led to this breakthrough discovery. They observed that a small section of shugoshin was identical to a segment of another protein they had previously studied in detail, called CTCF. Interestingly, CTCF also possesses the same molecular key that fits perfectly into the keyhole of cohesin, and it uses this mechanism to lock the cohesin rings as well, albeit in a different context. Additionally, cohesin also plays a role in compacting chromosomes by forming DNA loops, utilizing the same locking mechanism albeit in a different location.
"It appears that we have uncovered a universal mechanism that cells employ to shape DNA," notes Rowland. "What is even more remarkable is that CTCF and shugoshin may not be the only proteins that utilize these building blocks." According to Rowland and his colleagues in the UK, a range of critical proteins involved in regulating DNA appear to use the same molecular key to control cohesin. "By precisely timing and positioning the locking of cohesin on DNA, we can determine the precise shape of our chromosomes."
It is essential to bear in mind that DNA serves as the blueprint for life. The structure of DNA plays a critical role in dictating its function, which in turn impacts the behavior of our cells. As such, gaining a thorough understanding of DNA's structure could have significant implications for a wide range of scientific fields.
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