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Studies of telomerase-reactivated and aged ALT Naumovozyma castellii cells

Rodi, Stamatia Efthymia (2024) MOBN03 20232
Degree Projects in Molecular Biology
Popular Abstract
Can we fool the molecular time?

Cells in our body contain all the information needed for their structure and function, stored in the genetic material, the DNA. Like volumes of an encyclopedia, DNA is organized into chromosomes. Every time the cells divide, all chromosomes are copied, and each new cell gets one copy. But the copying mechanism is not perfect; the end parts of each chromosome -called telomeres- are not fully copied. Thus, in every cell division, telomeres get shorter and shorter. When this attrition reaches a critically short length, the cells cannot divide anymore, reaching senescence. This acts as a molecular clock, imposing a limit on the number of cellular divisions a cell can go through. And even if this sounds... (More)
Can we fool the molecular time?

Cells in our body contain all the information needed for their structure and function, stored in the genetic material, the DNA. Like volumes of an encyclopedia, DNA is organized into chromosomes. Every time the cells divide, all chromosomes are copied, and each new cell gets one copy. But the copying mechanism is not perfect; the end parts of each chromosome -called telomeres- are not fully copied. Thus, in every cell division, telomeres get shorter and shorter. When this attrition reaches a critically short length, the cells cannot divide anymore, reaching senescence. This acts as a molecular clock, imposing a limit on the number of cellular divisions a cell can go through. And even if this sounds problematic, it actually protects us from uncontrollable cell proliferation that could lead to tumorigenesis. However, some cells that are responsible for regenerating our tissues, as well as germ cells, have active mechanisms that counteract the telomeric length loss. These mechanisms are grouped into two main categories: one that depends on the action of the enzyme telomerase and one that uses the Alternative Lengthening of Telomeres pathways (ALT), although any potential interaction of these mechanisms remains unknown.

In this project we added telomerase in telomerase-deficient cells that have been using ALT, and we focused on the effects that this has on their phenotype and telomeric length. For this reason, we used the model organism Naumovozyma castellii, a budding yeast with a similar telomeric structure to human telomeres. Telomerase was reintroduced by mating -fusing- telomerase proficient and deficient cells. The derived mated cells were monitored for changes in their phenotype and telomeric structure.

Fascinatingly, we found that the introduced telomerase was active in the mated cells, elongating the telomeres. Furthermore, the telomeric length, growth rate, viability, replication potential, and colony size of the mated cells shifted from the ALT cell phenotype to the telomerase-proficient cells phenotype. These results suggest that cells can efficiently switch from the ALT-based to the telomerase-based elongation mechanism. Additionally, we concluded that in its presence, telomerase is the prevailing mechanism for telomere length maintenance.

Our results show that cells which lack telomerase can efficiently use it upon reintroduction. This opens a new horizon in regenerative medicine, as our somatic cells do possess the information for producing telomerase in their genome, even though they do not use it. Thus, it is possible that controllable expression of telomerase could counteract the molecular time signature on the telomeres. Aging is a natural process, but understanding the mechanisms that define it can provide us with a way of improving our quality of life during this journey.
Master’s Degree Project in Molecular Biology, 60 credits, 2024
Department of Biology, Lund University

Advisor: Dr. Marita Cohn, Dr. Héloïse Grunchec
Department of Biology, Lund University (Less)
Please use this url to cite or link to this publication:
author
Rodi, Stamatia Efthymia
supervisor
organization
course
MOBN03 20232
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9176127
date added to LUP
2024-10-04 15:37:02
date last changed
2024-10-04 15:37:02
@misc{9176127,
  author       = {{Rodi, Stamatia Efthymia}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Studies of telomerase-reactivated and aged ALT Naumovozyma castellii cells}},
  year         = {{2024}},
}