Related Experiment Video

Updated: May 10, 2026

Nucleoside Triphosphates - From Synthesis to Biochemical Characterization
15:22

Nucleoside Triphosphates - From Synthesis to Biochemical Characterization

Published on: April 3, 2014

TDP1 repairs nuclear and mitochondrial DNA damage induced by chain-terminating anticancer and antiviral nucleoside

Shar-yin N Huang1, Junko Murai, Ilaria Dalla Rosa

  • 1Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, Department of Radiation Genetics, Kyoto University Graduate School of Medicine, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, Japan, NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, NIH, Rockville, MD 20850, USA and Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.

Nucleic Acids Research
|June 19, 2013
PubMed

Insights

Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs DNA damage from chain-terminating nucleoside analogs (CTNAs). TDP1 is crucial for repairing both nuclear and mitochondrial DNA damage induced by these anticancer and antiviral drugs.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • Chain-terminating nucleoside analogs (CTNAs) are vital anticancer and antiviral agents.
  • The DNA repair mechanisms for CTNA-induced damage remain incompletely understood.
  • Nuclear and mitochondrial DNA integrity is essential for cellular function.

Purpose of the Study:

  • To investigate the role of tyrosyl-DNA phosphodiesterase 1 (TDP1) in repairing DNA damage caused by CTNAs.
  • To determine if TDP1 repairs damage in both nuclear and mitochondrial DNA.
  • To assess the impact of TDP1 deficiency on cellular sensitivity to CTNAs.

Main Methods:

  • Treatment of cells with four CTNAs: acyclovir (ACV), cytarabine (Ara-C), zidovudine (AZT), and zalcitabine (ddC).
  • Analysis of DNA damage accumulation and repair in wild-type and Tdp1-/- cells.
  • Assessment of mitochondrial DNA integrity and depletion following CTNA treatment.

Main Results:

  • TDP1 effectively removes covalently linked CTNAs from DNA 3'-ends.
  • Tdp1-/- cells exhibit hypersensitivity and increased DNA damage upon treatment with ACV and Ara-C.
  • Mitochondrial DNA depletion is exacerbated in Tdp1-/- cells treated with AZT and ddC.

Conclusions:

  • TDP1 plays a critical role in the repair of nuclear DNA damage induced by CTNAs.
  • TDP1 is essential for maintaining mitochondrial DNA integrity in the presence of certain CTNAs.
  • TDP1 is a key enzyme for cellular defense against CTNA-induced genotoxicity in both nuclear and mitochondrial compartments.

More Related Videos

Quantitative Detection of DNA-Protein Crosslinks and Their Post-Translational Modifications10:12

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

Published on: April 21, 2023

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage10:59

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

Related Concept Videos

Translesion DNA Polymerases02:10

Translesion DNA Polymerases

Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
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...
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview