In a new study, a team of Sydney scientists has made a groundbreaking discovery in telomere biology.
It has implications for conditions ranging from cancer to aging and heart disease.
Telomeres are DNA segments at the ends of every human chromosome. As we age, telomere length naturally decreases.
Over the course of a lifetime, telomere shortening instructs aging cells to stop dividing.
This normally functions as a critical barrier to stop cancer.
However, some people are born with abnormally short telomeres and suffer from bone marrow failure, pulmonary fibrosis and high rates of cancer.
Telomere length is also an important marker of disease risk for conditions such as cancer, heart disease and diabetes.
Telomere shortening causes chromosomes ends to resemble broken DNA.
However, it has remained a mystery why telomeres change from healthy to unhealthy with age. This research has identified the underlying cause.
The team found that when the telomere loop unfolds, the chromosome end is exposed and the cell perceives this as broken DNA.
It is not telomere length that matters, but telomere structure. The telomere loop becomes harder to form as telomeres get short.
Additionally, the team identified that telomeres can also change structure in response to some chemotherapeutic agents, which helps kill cancer cells.
The results of this study have also proven how important technological advances are in the field of research.
The lead author first developed his theories about telomere loops in 2002 when studying for his Ph.D.
However, the technology was not available at the time to easily visualize telomere loops using microscopy.
The advent of super-resolution microscopy, which was awarded the 2014 Nobel Prize in Chemistry, made it possible to see telomere loops with a microscope.
To complete this research, the team used super-resolution microscopes at four Sydney research institutions, and purchased the first Airyscan super-resolution microscope in Australia.
The team is only the second group in the world to see telomere loops with super-resolution microscopes and the first to determine their function.
The research project was led by Dr. Tony Cesare, Head of the Genome Integrity Unit at Children’s Medical Research Institute (CMRI) at Westmead, in collaboration with scientists from CMRI as well as UNSW Sydney’s Katharina Gaus.
The study is published online by Molecular Cell.
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Journal reference: David Van Ly et al. Telomere-loop dynamics in chromosome end protection, Molecular Cell (2018). DOI: 10.1101/279877