Telomere is a distinctive structure of repetitive nucleotide sequences found at the end of the body's chromosomes, which functions to stabilize the chromosome. In humans, telomere can reach a length of 15,000 base pairs. Each time a cell divides, some of the telomere is lost. When telomeres get too short, the cell no longer can divide and become inactive, a process that may lead to chromosome instability or cell death. Overall, telomere length is an indicator of cells' lifespan, which dictates key processes such as aging and cancer incidence.
Telomerase and Shelterin are known to bind to telomeres. Some scientists thought that these are the only proteins that can bind to telomeres. However, a new research shows there is another protein that can bind to telomeres -- Telomeric Zinc finger-Associated Protein (TZAP). The Scripps Research Institute researchers and collaborators find that TZAP regulates telomere length. The study appears in Science on 12 Jan 2017.
TZAP binds to long telomeres that have low level of shelterin -- a protein complex that shapes and safeguards human telomeres. TZAP triggers the process "telomere trimming" that causes the rapid deletion of telomeric repeats and therefore ensures that telomeres do not get too long.
According to study last author Eros Lazzerini Denchi, TZAP sets the upper limit of telomere length, which may prevent cells from proliferating too much.
Telomere shortening is double-edged. It induces replicative senescence and blocks cell division, which prevents cancer by limiting the number of cell divisions. But telomere shortening also affects the immunity of the body, which increases the risk of cancer. Moreover, defects in telomeres have been found in a series of aging-related disorders.
Collectively, TZAP is also a telomere-binding protein and regulates telomere length. "Binding of TZAP to long telomeres represents the switch that triggers telomere trimming, setting the upper limit of telomere length," the researchers wrote. The study is a breakthrough that could extend our understanding of telomere length regulation, and may lead to ways to combat telomere-related diseases.
In addition to Eros Lazzerini Denchi, other researchers of the study includes Julia Su Zhou Li, Javier Miralles Fuste, Tatevik Simavorian, Cristina Bartocci, Jill Tsai, and Jan Karlseder. Cusabio offers various proteins and other biomolecules, such as antibodies.