University of Edinburgh scientists have unraveled a long-standing mystery surrounding the preservation of centromeres during cell division. Their study, recently published in Science, reveals that the protein PLK1 plays a crucial role in coordinating key proteins at the right place and time, ensuring the centromere's correct location in newly formed cells.
“In the human body, around two trillion cells divide every day. Accurate chromosome segregation is the basis for life itself and mistakes can be catastrophic. If centromeres are missing or in the wrong place, then the genetic information is not shared correctly between the dividing cells. In adults, this can lead to many diseases including cancers, whilst in the earliest stages of life it can cause birth defects,” says Professor Jeyaprakash Arulanandam, who led the research team.
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The team employed biophysical, biochemical, structural and cell biology techniques to better understand PLK1 actions. They found that PLK1 initiates a series of chemical changes, known as phosphorylations, to proteins in the Mis18 complex and HJURP.
These modifications create binding sites and activate the Mis18 complex, which then guides HJURP to load CENP-A, a crucial protein for centromere identification, onto the centromeres at the correct time and place during cell division. This process ensures that CENP-A levels are replenished after each round of cell division, maintaining the centromere's integrity.
Pragya Parashara, first author of the study, likens this molecular process to a relay race, stating, "PLK1 kickstarts a molecular process similar to a relay race that determines how and when key proteins interact. It ensures that CENP-A levels are restored after each round of cell division, preserving the centromere’s integrity. This is one of cell’s most crucial safeguards and is vital to the correct transfer of genetic material through countless generations of cells, which is essential to the creation and maintenance of life."