September 2023: Martin Kupiec: Control of telomere length

A research led by Prof. Martin Kupiec, Edmond J. Safra member (Life Sciences) and his lab students, uncovered a basic molecular mechanism responsible for maintaining the length of the telomeres - the ends of the chromosomes - which are known to shorten during life.

The shortening of telomeres during cell replication also has exceptions: stem cells and embryonic cells. These cells are required to replicate many times. A human newborn, weighing about 3 kg, is created from a single cell that duplicates many times during pregnancy. Without control, the telomeres would shorten significantly even before birth, and to prevent this, an enzyme called telomerase is activated in these cells, which lengthens the telomeres and prevents them from shortening.

The research was carried out in a model of yeast cells, which are used in many experiments because they are very similar to human cells but grow much faster and are accessible for research work. Also, similar to embryonic cells, yeast contains active telomerase. The researchers focused on proteins that are known to play a central role in the DNA replication mechanism, and found that a ring molecule called PCNA acts, together with a telomeric protein complex, the CST, activate telomerase, thus coordinating its activity with the duplication of the genome. Mutations in the CST complex cause a severe and incurable genetic syndrome called Coats plus, in which most sufferers do not reach adulthood.

This is fundamentally basic research, but it may lead to the development of treatments in many areas, including cancer, where cells replicate rapidly, and aging - related to the shortening of the telomeres.

The article was published in the journal eLife.