These CENP-A proteins ensure that divided genetic information is kept intact during mitosis.
Biologists in Europe and the U.S. have pinpointed a secret that powers the human body's gene replicating ability. These areas, called centromeres, are responsible for billions and billions of perfect DNA matches made over the course of our lifetimes, ensuring that cells can divide successfully. And when they don't -- that's when conditions like cancer take hold. The centromere has a lot resting on its microcellular shoulders.
For decades, scientists have wondered what exactly is holding these complex reactions together.... literally. Now, a team of scientists -- including corresponding author A. Arockia Jeyaprakash (also sometimes referred to as Jeyaprakash Arulanandam online) and more than a dozen others -- has found that the enzyme PLK-1 is responsible for the centromere's incredibly high success rate in replicating our genes from cell to cell. The results of their study appear now in the peer-reviewed journal Science.
Scientists have known that PLK-1 (short for polo-like kinase 1) is produced by a specific genetic code of its own. Study of it dates back at least 30 years, and its role in the cell is to help process the major cellular energy sources ATP and ADP. But it was the gene's role in cancer that first got scientists' attention, because PLK-1 -- as a signature of its gene -- is found in tumors of cancers of the lung, colon, stomach, and esophagus, among others.
Cancer works by leveraging the body's existing efficient processes into creating new, unrelated cells that are harmful. It's like taking the gas pump delivering fuel into your car's tank and pointing it toward a forest fire. The fuel pump is still doing its designated job, and it has no sense of the difference in outcomes, but the results will be disastrous nontheless. The fact that PLK-1 endures in the cells of tumors shows that it endures in general, and is involved in mitosis (the division of cells for replication) under even extreme body conditions like neoplastic (tumor) growth.
When a cell divides, the double helix of DNA is divided, as well. Centromeres coordinate the precise, nearly perfect matchmaking of the separated strands with their associated enzymes in each new cell. But who's watching the watcher, as they say? How is the centromere so persistent, despite being copied and copied and copied? Well, it turns out that PLK-1 restocks vital materials that indicate the centromere is ready to take action.
To do this, PLK-1 uses a reaction called phosphorylation, meaning that it adds a molecule called a phosphate to an existing protein. Phosphates -- represented by the common version phosphoric acid (HPO) or the simplest form PO -- work like switched that turn a protein's behavior on or off from its previous position. By phosphorylating two specific protein groups involved in the centromere, PLK-1 functionally creates a queue of the protein that the centromere actually needs, known as CENP-A. These CENP-A proteins then line up to ensure that individual chromosomes are kept organized as they're separated and migrated, like a camp counselor keeping tabs on children who split from their "buddy pairs" to use the restroom.
Previous work showed the involvement of PLK-1 in this reaction (including work by the same team on one of the proteins that PLK-1 is phosphorylating), but scientists did not understand the chemical reactions themselves. In a University of Edinburgh statement, Jeyaprakash described the process as a "relay race" to ensure that enough CENP-A is present for a working centromere area. In that sense, Jeyaprakash said, the entire chain of events is "essential to the creation and maintenance of life." Each piece plays a vital role -- literally.