Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Telomeres and Telomerase02:41

Telomeres and Telomerase

23.6K
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
23.6K
Biosynthesis of Nucleic Acids01:28

Biosynthesis of Nucleic Acids

94
Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
94
Replication in Eukaryotes01:29

Replication in Eukaryotes

14.1K
In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
14.1K
Replicative Cell Senescence02:15

Replicative Cell Senescence

3.7K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.7K
Functions of Thyroid Hormones01:18

Functions of Thyroid Hormones

2.9K
The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
2.9K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

9.2K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.2K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Saturating variant analysis of TERC redefines the human telomerase reverse transcription mechanism.

bioRxiv : the preprint server for biology·2026
Same author

Primer- and template-independent RNA polymerization by terminal nucleotidyltransferase TENT4B.

bioRxiv : the preprint server for biology·2026
Same author

Therapeutic 6-thio-deoxyguanosine inhibits telomere elongation in cancer cells by inducing a non-productive stalled telomerase complex.

Nature communications·2025
Same author

Extension of replicative lifespan by synthetic engineered telomerase RNA in patient induced pluripotent stem cells.

Nature biomedical engineering·2025
Same author

Metabolic constraint of human telomere length by nucleotide salvage efficiency.

Nature communications·2025
Same author

Successful cord blood transplantation for del7q myelodysplastic syndrome in Pearson marrow pancreas syndrome.

American journal of hematology·2023

Related Experiment Video

Updated: Aug 5, 2025

Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence
12:08

Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence

Published on: May 22, 2013

46.6K

Thymidine nucleotide metabolism controls human telomere length.

William Mannherz1,2,3, Suneet Agarwal4,5,6

  • 1Division of Hematology/Oncology and Stem Cell Program, Boston Children's Hospital, Boston, MA, USA.

Nature Genetics
|March 24, 2023
PubMed
Summary

Human telomere length is controlled by thymidine (dT) nucleotide metabolism. Manipulating dT metabolism, such as through dT supplementation or SAMHD1 inhibition, can restore telomere length, offering therapeutic potential for degenerative diseases.

More Related Videos

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
08:34

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

10.4K
Author Spotlight: Optimization of Performance Parameters of the TAGGG Telomere Length Assay
08:23

Author Spotlight: Optimization of Performance Parameters of the TAGGG Telomere Length Assay

Published on: April 21, 2023

3.0K

Related Experiment Videos

Last Updated: Aug 5, 2025

Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence
12:08

Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence

Published on: May 22, 2013

46.6K
Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
08:34

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

10.4K
Author Spotlight: Optimization of Performance Parameters of the TAGGG Telomere Length Assay
08:23

Author Spotlight: Optimization of Performance Parameters of the TAGGG Telomere Length Assay

Published on: April 21, 2023

3.0K

Area of Science:

  • Genetics
  • Molecular Biology
  • Biochemistry

Background:

  • Telomere length is crucial for human health, influencing lifespan and disease susceptibility.
  • The genetic factors regulating telomere length are not fully understood.
  • Thymidine nucleotide metabolism's role in telomere maintenance requires further investigation.

Purpose of the Study:

  • To identify genetic determinants of human telomere length.
  • To investigate the impact of thymidine nucleotide metabolism on telomere maintenance.
  • To explore therapeutic strategies for telomere-related disorders.

Main Methods:

  • Genome-wide CRISPR-Cas9 screening for telomere length regulation.
  • Targeted gene disruption of thymidine metabolism pathway genes (TK1, TYMS, SAMHD1).
  • In vitro assays of telomerase activity and dT supplementation experiments.

Main Results:

  • CRISPR screening identified thymidine (dT) nucleotide metabolism as a key regulator of telomere length.
  • Decreasing dT salvage (TK1) or de novo production (TYMS) shortened telomeres.
  • Inactivating SAMHD1 or supplementing with dT significantly elongated telomeres.
  • Thymidine triphosphate directly stimulated telomerase activity in vitro.
  • dT supplementation or SAMHD1 inhibition restored telomeres in patient-derived cells.

Conclusions:

  • Thymidine nucleotide metabolism critically controls human telomerase activity and telomere length.
  • Modulating thymidine metabolism presents a potential therapeutic avenue for genetic telomere biology disorders and degenerative diseases.