Related Experiment Video

Updated: Jul 11, 2025

Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications
10:12

Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications

Published on: April 21, 2023

2.8K

TDP1 suppresses chromosomal translocations and cell death induced by abortive TOP1 activity during gene transcription

Diana Rubio-Contreras1,2, Fernando Gómez-Herreros3,4

  • 1Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013, Seville, Spain.

Nature Communications
|November 9, 2023
PubMed

Insights

DNA topoisomerase I (TOP1) can cause DNA breaks, leading to genome rearrangements. Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs these breaks, preventing transcription-associated translocations and maintaining genome stability.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • DNA topoisomerase I (TOP1) relieves DNA torsional stress by transiently nicking one DNA strand.
  • Abortive TOP1 activity can create persistent protein-linked single-strand breaks (SSBs).
  • Tyrosyl-DNA phosphodiesterase 1 (TDP1) initiates repair of TOP1-induced SSBs by detaching the TOP1 peptide.

Purpose of the Study:

  • To identify double-strand breaks (DSBs) arising from TOP1-induced SSBs as a source of genome rearrangements.
  • To elucidate the mechanism of transcription-associated chromosomal translocation formation.
  • To demonstrate the role of TDP1 in suppressing these genomic instabilities.

Main Methods:

  • Investigating DNA repair pathways.
  • Analyzing genome rearrangement formation.
  • Studying transcription-associated DNA damage.
  • Utilizing genetic and biochemical assays.

Main Results:

  • TOP1-induced SSBs can lead to DSBs during replication or transcription.
  • These DSBs are a source of genome rearrangements, including chromosomal translocations.
  • TDP1 suppresses these rearrangements through an error-prone pathway involving the MRN complex and non-homologous end-joining.
  • TDP1 is crucial for protecting gene transcription and genome stability.

Conclusions:

  • TOP1-induced DSBs pose a significant threat to genome stability, particularly during transcription.
  • TDP1-dependent end-joining is essential for preventing transcription-associated translocations.
  • The study highlights TDP1's critical role in maintaining genomic integrity.

More Related Videos

Real-Time Quantification of the Effects of IS200/IS605 Family-Associated TnpB on Transposon Activity04:04

Real-Time Quantification of the Effects of IS200/IS605 Family-Associated TnpB on Transposon Activity

Published on: January 20, 2023

2.4K
Inducible and Reversible Dominant-negative DN Protein Inhibition08:35

Inducible and Reversible Dominant-negative DN Protein Inhibition

Published on: January 7, 2019

8.4K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.8K
Transcription Attenuation in Prokaryotes02:42

Transcription Attenuation in Prokaryotes

Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure.  Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
15.3K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.4K
DNA Damage can Stall the Cell Cycle02:37

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...
9.2K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.4K