Scientists have discovered a new telomeric DNA structure

Telomeres are sometimes considered the key to living longer. They protect genes from damage but get shorter each time a cell divides. Each time a cell divides, the telomeres become slightly shorter. Eventually they become so short that the cell can no longer divide successfully and the cell dies.

Little is known about the structure of telomeric chromatin at the molecular level. In a new study, scientists from the Leiden Institute of Physics (LION) have discovered a new telomeric DNA structure. They used physics methods for biological experiments and a tiny magnet for discovery.

Since the DNA between telomeres is two meters long, it must be folded to fit in a cell. This is done by wrapping bundles of protein and DNA together to form a structure known as the nucleosome. A nucleosome, a free (or unbound) DNA fragment, a nucleosome, etc. are arranged in a pattern similar to a string of beads.

The string of pearls then contracts even more. The length of the DNA between the nucleosomes – the beads on the chain – determines how it gets there. There were already two known post-folding structures. One of them has free DNA hanging in the space between two neighboring beads that hook together (Fig. 2A). Neighboring beads fail to bond if the DNA gap between them is too small. Then two stacks begin to form side by side.

In this study, the scientists discovered another telomere structure: the nucleosomes are much closer together, so there is no more free DNA between the beads. This ultimately creates a large helix, or spiral, of DNA.

The scientists discovered this new structure using a combination of electron microscopy and molecular force spectroscopy. This last technique comes from the laboratory of Van Noort. Here, one end of the DNA is attached to a glass slide and a small magnetic ball is stuck to the other.

A set of strong magnets above this ball then separates the pearl necklace. By measuring the force needed to pull the beads apart one at a time, you will know more about how the string is bent. The Singapore researchers then used an electron microscope to better understand the structure.

Van Noort said, “Structure is “the holy grail of molecular biology. Knowing the structure of molecules will allow us to better understand how genes are activated and deactivated and how cell enzymes process telomeres: how they repair and copy DNA, for example. The discovery of the new telomeric structure will improve our understanding of the building blocks of the body. And that, in turn, will ultimately help us study aging and diseases like cancer and develop drugs to fight them.

Journal reference:

  1. Soman, A., Wong, SY, Korolev, N., et al. Columnar structure of human telomeric chromatin. Nature (2022). DOI: 10.1038/s41586-022-05236-5

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