8. Apr. 2024

A study led by scientists from CEITEC Masaryk University and Institute of Biophysics of the Czech Academy of Sciences has shown how the elimination of the FAS1 protein and the KU70/80 protein complex in plants affects the length of their telomeres, which serve to protect the ends of chromosomes. Their research is the latest contribution to a better understanding of the key processes that control the viability of cells and whole organisms and involved a team of Czech scientists from three research institutes.

Every cell in the human body, animals, plants and fungi contains unique genetic information in its nucleus, written in four letters - A, T, C and G. These are the building blocks that make up the DNA chain. Two related strands of DNA then sit together, forming a zipper-like connection, and in this form the DNA is further coiled into a structure known as a chromosome, in which the DNA is linked to a series of proteins, primarily histones. At some stages in the life of a cell, the chromosome can be thought of as two taut shoelaces crossed at one point. And just as shoelaces have stiffened ends, we find similar sections at the ends of chromosomes with protective functions - telomeres - that help chromosomes stay whole and functional for longer time. Telomeres are often referred to as markers of ageing, because during ageing the length of telomeres gradually shortens (this is true for most cells in the human body, for example) and their protective function changes depending on their length and the binding of specific proteins.

A team of scientists from five research institutes focused on these ends in plants and investigated the degree of mutual influence of two factors, whose individual knockout has a completely opposite effect on telomere length.

The FAS1 protein facilitates the packaging of DNA immediately after it is copied (replicated) into a folded form with a complex of proteins – histones. It is also involved in DNA repair, and its knockout commonly results in significant telomere shortening and impaired plant viability, and is even fatal in animals. In plants, it causes complications with growth, seed formation and often premature death. These effects are even transmitted to the next generation of plants and can be observed with the naked eye.

The second player is the KU70/80 protein complex, which can repair double-strand breaks in DNA while protecting the extreme ends of telomeres so that they are not mistaken for DNA breaks that need to be repaired. It also prevents alternative methods of telomere lengthening. Knocking out this 'defender' causes a significant lengthening of the telomeres in plants, which, however, has no significant effect on the appearance and viability of the plants. "Experiments in a model organism (Arabidopsis thaliana/thale cress), in which we eliminated the function of both these players (FAS1 and KU70) simultaneously, showed that they have opposing effects on telomere length regulation. However, knocking out KU70 activity has a dominant effect on telomere length," says Michal Závodník. "Moreover, KU70 knockout can also suppress the telomere shortening that results from knocking out the activity of the counterpart (FAS1). The different intensity of the impact of knocking out one player and the other leads to different telomere lengths, but these are longer compared to plants with normal function of both proteins," adds Prof. Jiří Fajkus.

Immediately adjacent to the telomeres, genes for ribosomal RNA production are found on two chromosomes of the thale cress. These are tandemly arranged in several hundred copies, and the same team from Masaryk University has previously described that FAS1 knockout results in a gradual loss of these copies, similar to the loss of repetitive stretches of telomere DNA. Unlike telomeres, however, loss of function of the KU70 protein in plants with knocked-out FAS1 function had no significant effect on the progressive loss of genes for ribosomal RNA production. 

Thanks to this research, it was possible to reveal the intensity of the influence and the functional interconnection of the processes involving both FAS1 and KU70. The work of the research team thus contributes to a better understanding of the interconnection and regulation of processes essential for maintaining the viability of cells and organisms – i.e. DNA replication, chromatin assembly, DNA damage repair and telomere maintenance.

The research has been published in The Plant Journal and funded by GACR projects (20-01331X, 23-06643S) and GAMU MUNI/R/1364/2023.

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