Cell biologists decipher signal that ensures no chromosome is left behind

Begins as a single cell, and organisms undergo millions of generations of divisions to eventually generate the bones, heart, brain, and other components that make up a living being. The most important source in this complex process is the transfer of DNA by each subsequent cell division into separate packets called chromosomes.

It is critical that all chromosomes are duplicated and precisely distributed by each generation of cell division. If the hereditary chromosome components change, even slightly, it can result in birth defects and certain cancers.

A new study published in the journal Science by postdoctoral fellow Pablo Lara-Gonzalez, Division of Biological Sciences, Professor Arshad Desai and their colleagues, addresses the mystery of how chromosomes are inherited correctly each time a cell divides. Using a new probe that monitors an important aspect of this process, Lara-Gonzalez and Desai set out the mechanics behind a ‘wait’ signal that ensures cell division is not initiated prematurely.

The researchers concentrated their investigations on a pathway in the cell, the ‘pivot point’, which is a kind of quality control mechanism that ensures accurate inheritance of chromosomes during cell division. The pivot point of the pivot point is activated at a location on the chromosome called kinetochore, a mechanical interface where protein fibers are linked to pull chromosomes apart.

“When kinetochores are not attached to these protein fibers, it sends a ‘wait’ signal that stops the cell in mitosis (cell division) and thus gives time to form attachments,” said Desai, a professor in the cell division. , said. and Developmental Biology (Biological Sciences) and the Department of Cellular and Molecular Medicine (School of Medicine). “In this way, the cell ensures that all chromosomes are properly fixed and ready to be pulled apart before the cell divides, leaving no chromosome behind.”

In the Science paper, the researchers describe how the guard checkpoint signal is specifically generated in kinetochores of unlinked chromosomes. Carefully, they developed a fluorescent probe that enabled them to see for the first time the major molecular event in growth signaling in kinetochores in living cells.

“This work has identified an important ‘matchmaker’ molecule that brings together two components of the wait signal that do not like to associate with each other on their own,” Lara-Gonzalez said. “These findings help explain why the ‘wait’ checkpoint signal is selectively generated at kinetochores and not elsewhere in the cell.”

The findings provide a framework for ways in which the accuracy of chromosome inheritance can be reduced in certain disease states, such as cancer, the researchers said.