Telomeres, the complexes that protect the ends of eukaryotic chromosomes, are composed of repetitive DNA sequence bound by specialized proteins; in vertebrate the telomeric TTAGGG repeats are bound by the Shelterin and the CST complexes. Telomeres can form special protective structures such as G-quadruplexes and telomere (t)-loops.

 

With each cell division, telomeres shorten. Upon reaching a critical threshold, they activate the DNA damage response causing cell cycle arrest to protect the genome integrity and limit cell proliferation, thus inhibiting cancer, but also accelerating aging-associated pathologies. Paradoxically, short telomeres can also induce genomic instability and increase the risk for cancer transformation. To extend their proliferation capacity, germ cells, stem cells and most cancers elongate their telomeres by the telomerase a ribonucleoprotein complex.

 

We, in the Tzfati laboratory, are studying fundamental questions in the telomere field, focusing on:

• The role of the helicase RTEL1 in telomere biology and disease

• Mouse models for telomere biology

• Telomerase RNA structure and function

• Telomeres and reproductive aging