Nature corrects the textbook description of "telomeres"!

Scientists at Nanyang Technological University in Singapore have mapped out the molecular structure of chromosomes known as the key parts of telomeres, which play a key role
in aging and cancer.

The Nanyang Technological University team found that telomeres are arranged in columns
like springs.
They also found that telomeres' shape exposed a portion of the DNA to the outside world, leaving it unprotected, making it more vulnerable to damage
than previously thought.
The researchers say their advances in genetic research will help explain why
humans age and develop cancer.
Telomeres are protective caps
at the ends of the DNA molecules that make up our chromosomes.
Like the plastic tip at the end of the shoelace, the function of telomeres is to protect the ends of chromosomes from damaging themselves
due to mutual adhesion or wear.
Previously, due to the chemical instability and complex reproducibility of telomere DNA, it was difficult for scientists to replicate enough telomere DNA in the lab to be able to observe its structure
using an electron microscope.

In their study, published this month in the journal Nature, the researchers tweaked the existing process of replicating DNA and found that in telomeres, nucleosomes contain tightly arranged strands of DNA (DNA that are stacked
in columns around chromosomal proteins called histones).

Lars Nordenski&ouml, Dean of the School of Biological Sciences, Nanyang Technological University; Professor ld, who led the study, said: "Our study shows that the structure of telomeres is not the zigzag described in textbooks, but rather cylindrical and spring-like
.
This exposes a key part of DNA — its spiral — to the outside
.
This helps us understand that while telomeres play a vital role in preventing DNA damage, they are themselves hotspots
for DNA damage.
Our research will help researchers and doctors understand the reasons behind telomere damage at the molecular level, as detailed studies of DNA structure and external factors such as proteins and other cellular processes are very limited
.
”

This research represents a potential biological advance in understanding how the human body ages and becomes susceptible to disease, reflecting NTU's commitment to addressing the needs and challenges of healthy living and ageing, one of
the four human challenges that NTU seeks to address through its 2025 Strategic Plan.
To get their results, the researchers used state-of-the-art cryo-electron microscopy from the Institute of Structural Biology at Nanyang Technological University to probe the structure
of telomeres.

In addition to deepening understanding of how telomeres are involved in processes such as aging and DNA damage, the findings of the Nanyang Technological University research team may also help develop potential treatments
for diseases caused by telomere dysfunction.
These disorders include aplastic anemia (the body stops producing enough new blood cells), congenital keratosis (a rare inherited form of bone marrow failure, and the inability of the bone marrow to produce enough blood cells, often leading to death before the age of 30).

Dr Aghil Soman, a researcher at NTU's School of Biological Sciences and co-author of the study, said: "The future focus of our DNA research will be on how our DNA structure interacts with previously discovered telomere-specific factors, with a focus on
factors related to cancer development and longevity.
Our structure also provides a pathway
to improve small molecule anti-cancer drugs.
With the structure of the telomere nucleosome combination, it is now possible to design anticancer drugs
that target only high-affinity telomeres.
This will help overcome the limitations of drugs such as cisplatin, which, while killing cancer cells in humans, can also cause damage
to the kidneys, liver, and brain.
”

Nordenskiö Professor ld added: "This study reveals the tissue of telomere proteins at the molecular level, paving the way
for further structural studies.
This can reveal the structure-function relationship
of telomeres in the context of aging and cancer.
It can also provide a template
for the development of treatments for genetic diseases.
From our study, we also found elegant grooves formed by DNA, which indicates possible remodeling
within telomeres.
This could provide a future platform
for drug research targeting damage at telomere levels.
”

Columnar structure of human telomeric chromatin.
Nature, 2022; 609 (7929): 1048