Nanyang Polytechnic in Singapore mapped electron microscopy of the molecular structure of chromosome telomeres DNA

Scientists at Nanyang Technological University in Singapore have created electron microscopy pictures of the molecular structure of chromosomal telomeres, which play a key role
in aging and cancer.
The team found that the components of telomeres are arranged like springs in cylindricals, and that the shape of telomeres exposes a portion of the DNA 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 the terminal structures of eukaryotic chromosomes that make up the protective cap
at the end of our chromosome DNA molecules.
Like the plastic head 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, play a key role in aging and cancer, and are also targets for DNA damage and DNA damage responses
.
Previously, due to the chemical instability and complex reproducibility of telomere DNA, we knew very little
about the structure of telomere chromatin at the molecular level.
Scientists failed to observe its structure
with an electron microscope in the laboratory.

Researchers at Nanyang Technological University in Singapore used negative chromochromomicroscopy and single-molecule magnetic forceps to characterize 3-kbp long telomere chromatin fibers and obtained a cryo-electron microscopy structure
of compressed telomere tetranuclear bodies and their dikaryotes.
The structure shows that the nucleosomes are tightly stacked in a columnar arrangement, and the nucleosomes repeat length is unusually short, consisting of DNA of about 132 bp, forming a continuous supercoil
around the histone octrimer.
This columnar structure is mainly stabilized
in a synergistic manner by the H2A carboxyl terminal and the histone amino terminal tail.
The columnar conformation results in a DNA helix exposure, which may make it susceptible to DNA damage and DNA damage responses
.
This conformation also exists in another open state, where one of the nucleosomes is not stacked and flipped, exposing acidic regions
on the histone surface.
The structural features revealed in this study suggest the mechanism
by which protein factors involved in telomere maintenance approach telomere chromatin in their compact form.
The article was published in Nature in the middle of this month
.

Professor Lars Nordenskiöld, Dean of the School of Biological Sciences at Nanyang Technological University, led the study, saying: "Our study shows that the structure of telomeres is not zigzag as described in textbooks, but rather columnar and spring-shaped
.
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.
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 (when 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 (which usually leads 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 and will 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.
”

Professor Nordenskiöld 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.