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Related Concept Videos

Telomeres and Telomerase02:41

Telomeres and Telomerase

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 DNA.
Telomeres and Telomerase02:41

Telomeres and Telomerase

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 DNA.
Replication in Eukaryotes01:29

Replication in Eukaryotes

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...
Replication in Eukaryotes02:31

Replication in Eukaryotes

Overview
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

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...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

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...

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Optimization of Performance Parameters of the TAGGG Telomere Length Assay
08:23

Optimization of Performance Parameters of the TAGGG Telomere Length Assay

Published on: April 21, 2023

Probing the telomere damage response.

Rekha Rai1, Sandy Chang

  • 1Department of Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Methods in Molecular Biology (Clifton, N.J.)
|April 5, 2011
PubMed
Summary
This summary is machine-generated.

Telomere dysfunction triggers DNA damage responses, activating key sensors and kinases. Detecting telomere dysfunction-induced foci (TIFs) helps quantify damage and monitor signaling pathways.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Telomere attrition and shelterin inhibition trigger DNA double-stranded breaks (DSBs).
  • The DNA damage repair (DDR) pathway recognizes these telomeric DSBs.
  • This recognition activates checkpoint sensors and signaling kinases.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying telomere dysfunction detection.
  • To characterize the DNA damage response at dysfunctional telomeres.
  • To establish a method for quantifying telomere dysfunction.

Main Methods:

  • Induction of telomere dysfunction via TRF2 deletion or TPP1(ΔRD) expression.
  • Detection of DNA damage response markers like γ-H2AX and 53BP1.
  • Formation and observation of telomere dysfunction-induced foci (TIFs).

Main Results:

  • Dysfunctional telomeres are recognized as DSBs by the DDR pathway.
  • Activation of DDR sensors (MRN, γ-H2AX, 53BP1) and kinases (ATM, ATR, Chk1, Chk2, p53).
  • Formation of TIFs through the association of γ-H2AX and 53BP1 with dysfunctional telomeres.

Conclusions:

  • Telomere dysfunction elicits a robust DNA damage response.
  • TIFs serve as a quantifiable marker for telomere dysfunction.
  • Monitoring TIFs allows for assessment of signaling pathway activation in response to telomere damage.