New Insights into Chromosome End Maintenance

A recent Weill Cornell Medicine study published in Nucleic Acids Research sheds light on how cells maintain chromosome ends during division, a critical process for cellular health. The preclinical research, conducted using yeast, focuses on protein interactions that regulate telomerase, an enzyme essential for preventing uncontrolled cell division or premature aging.

The study centered on the three-protein CST complex and the DNA polymerase α/primase (PP) complex. Senior author Neal Lue stated, "We found that DNA polymerase α is recruited to chromosome ends and forms an assembly with the CST complex. This both regulates telomerase activity and protects chromosome ends from damaging repairs.”

The team introduced mutations that disrupted CST-PP interactions and observed varying outcomes. Dr. Lue noted, "Our data suggest that bringing in the CST-PP complex is a critical step in terminating telomerase activity." Some mutants exhibited telomeres growing longer without DNA damage, while others showed slow growth, telomere length variations, and single-stranded DNA overhang accumulation. First author Eun Young Yu added, “Our study provided the first in vivo evidence that PP is not only making DNA at telomeres, but also protecting them.”

These findings could advance the understanding of telomere biology disorders. Dr. Lue explained, “Mutations that upregulate telomerase activity are common in all types of cancers. In order for cancer cells to proliferate indefinitely, they need to activate telomerase to lengthen short telomeres.” Thus, altering CST protein activity with drugs could inhibit cancer cell growth by changing the lengths or protection status of telomeres. Targeting CST proteins also could help patients overcome resistance to some cancer medications.