The findings offer new insights into cell health and disease as failures in replication licensing can result in cell death or cancer.for replication also keeps the replication process in check, thus solving a long-standing mystery in biology. The research was recently published in the journalThe cells of humans and all other higher organisms employ a sophisticated system of checkpoints and licensing proteins to guarantee accurate replication of their genomes prior to division.
Figuring out how cells avoid that fate has been tricky. “We needed to be studying events in the first minutes of the DNA synthesis phase of the cell cycle, so it’s a very transient period,” said first author Nalin Ratnayeke, a graduate student who worked on this project both at Stanford University and at Weill Cornell Medicine in Dr. Meyer’s lab. The lab moved to Weill Cornell Medicine in 2020.
To confirm their results, the scientists collaborated with colleagues at the Medical Research Council in Cambridge, UK, who found that the inhibitory mechanism can be recapitulated in a simplified system that reproduces the entire DNA synthesis process with purified components in a test tube. “That allowed us to reconstitute all the components for DNA synthesis, and to prove that CMG helicase is directly inhibited by CDT1,” said Dr.
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