Scientists discover mechanism that preserves centromere during cell division

Scientists have solved a decade-old question about the mechanism that preserves the centromere, the center that ensures the correct division of DNA during cell division.

The study, published in Sciencerevealed that a protein, known as PLK1, triggers a process that coordinates key proteins to the right place at the right time during cell division, ensuring that each new cell has a centromere in the right place.

The centromere is a region of DNA where the cell division machinery attaches to separate identical copies of the cell’s genetic material into newly formed cells.

This discovery sheds light on one of the most fundamental processes in life, which ensures that the cell’s DNA, packaged in chromosomes, is properly segregated over multiple rounds of cell division.

“In the human body, about two trillion cells divide every day. The precise segregation of chromosomes is the basis of life itself, and errors can be catastrophic. If centromeres are missing or in the wrong place, genetic information is not shared correctly between dividing cells.

“In adults, this can lead to many diseases, including cancers, while in early life it can cause birth defects,” says Professor Jeyaprakash Arulanandam, who led the work at the University of Edinburgh and Ludwig-Maximilians-University of Munich.

The cell division mechanism identifies centromeres by the presence of multiple copies of a protein called CENP-A. But with each cell division, the stocks of this protein in the centromeres must be replenished.

Over the years, the precise molecular events that allow this replenishment to occur so that the centromere maintains its identity and location across large numbers of cell divisions have been the subject of intense research.

Research by another group previously revealed that PLK1 is one of the “master” molecular switches that controls when CENP-A replenishment occurs, but its mechanism of action remains a mystery.

The team, including researchers from the University of Edinburgh and Ludwig-Maximilians-University of Munich, used biophysical, biochemical, structural and cell biology techniques to better understand the actions of PLK1.

This study revealed that PLK1 performs a chemical change, called phosphorylation, on two proteins, called Mis18α and Mis18BP1, which are part of a set of proteins called the Mis-18 complex.

Previous research, including that led by Professor Jeyaprakash Arulanandam’s team, has revealed that the Mis18 protein complex plays a critical role in replenishing CENP-A levels when cells divide.

These initial chemical changes create binding sites on the Mis18 complex, allowing the PLK1 protein to perform additional phosphorylations on other Mis18 proteins that activate the Mis18 complex.

The researchers found that PLK1 also phosphorylates another protein, known as HJURP, which is responsible for loading CENP-A onto centromeres.

Together, these changes allow the Mis18 complex to act as a guide, controlling when HJURP binds to the centromere and ensuring that CENP-A is loaded into the right place at the right time during cell division.

“PLK1 triggers a relay race-like molecular process that determines how and when key proteins interact. It ensures that CENP-A levels are restored after each round of cell division, thereby preserving centromere integrity.

“This is one of the most crucial protective measures of cells and is essential for the proper transfer of genetic material through countless generations of cells, which is essential for the creation and maintenance of life,” said Pragya Parashara, one of the study’s lead authors at the University of Edinburgh.