Cell cycle checkpoints found to do double duty, according to researchers at the State University of New York
Researchers at SUNY Upstate Medical University have found that cell-cycle checkpoints may do double duty in preventing cells from irregular replication, which leads to cancer.
David M. Gilbert, Ph.D., associate professor of biochemistry and molecular biology at SUNY Upstate, found that when cells experience conditions that make it difficult for them to finish duplicating their DNA, "checkpoint" controls not only shut down the replication process, but may also be required to actively maintain the integrity of the partially replicated DNA strands. Defective checkpoints controls could explain why some individuals have genetic pre-dispositions to cancer, said Gilbert. The study was reported in the October issue of Nature Cell Biology.
Gilbert uses the following analogy to explain his finding: "If factory A is making a widget and all of sudden the mechanics fail and threaten the widget's development, the checkpoint sends out a signal to halt all further production and hold all the pieces of the partially assembled widget in place until the factory receives the go ahead to continue making the widget.
Gilbert's research is significant for another reason. Previously researchers found that cell-cycle checkpoints that shut down the replication process had existed in yeast. "Now we have a solid foundation to link single-cell organisms [yeast] to humans, and the confidence to look at the research that has been done with yeast and know that it is relevant to humans," he said.
"However, replication shut down was not in itself sufficient to explain why checkpoint defects lead to cancer," Gilbert noted. "The real surprise was that, in the absence of checkpoint controls, the cellular factories that duplicate DNA fall apart. Without the ability to complete the replication process, information contained within the DNA becomes lost, increasing the risk that cancer causing mutations will occur."
Gilbert suggested that knowing the fundamental steps that enable the faithful duplication of DNA in all cell types may allow the development of therapeutic approaches that treat the common denominator of cancer as a whole, rather than requiring different treatments for different types of cancer.
Gilbert was aided in his research by one of his post-doctoral associates, Daniela S. Dimitrova, Ph.D.