Related Experiment Video

Updated: Aug 12, 2026

CD Spectroscopy to Study DNA-Protein Interactions
06:48

CD Spectroscopy to Study DNA-Protein Interactions

Published on: February 10, 2022

Transcription-dependent degradation of topoisomerase I-DNA covalent complexes

Shyamal D Desai1, Hui Zhang, Alexandra Rodriguez-Bauman

  • 1Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.

Molecular and Cellular Biology
|March 18, 2003
PubMed

Insights

Topoisomerase I (Top I)-DNA complexes stall RNA transcription, triggering proteasome-mediated degradation of Top I and RNA polymerase II. Transcription recovery relies on this degradation and transcription-coupled repair (TCR).

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • DNA Repair Mechanisms

Background:

  • Topoisomerase I (Top I)-DNA covalent complexes are unique DNA lesions.
  • The repair and processing mechanisms of these complexes are not fully understood.

Purpose of the Study:

  • To investigate the impact of Top I-DNA covalent complexes on RNA transcription.
  • To elucidate the cellular response and recovery mechanisms following transcription arrest by Top I-DNA complexes.

Main Methods:

  • Studied Topoisomerase I (Top I)-DNA covalent complexes in normal nontransformed cells.
  • Analyzed RNA transcription, proteasomal degradation pathways, and transcription-coupled repair (TCR).

Main Results:

  • Top I-DNA covalent complexes transiently arrest RNA transcription.
  • Transcription arrest activates proteasomal degradation of Top I and RNA polymerase II.
  • Transcription recovery is dependent on Top I degradation and functional TCR.

Conclusions:

  • Top I-DNA complex-induced arrest of RNA polymerase II elongation triggers a proteasome-mediated signaling pathway.
  • This pathway leads to the degradation of both Top I and RNA polymerase II.
  • Proteasomal degradation precedes TCR-mediated repair of single-strand breaks.

More Related Videos

Simple and Fast Rolling Circle Amplification-Based Detection of Topoisomerase 1 Activity in Crude Biological Samples10:13

Simple and Fast Rolling Circle Amplification-Based Detection of Topoisomerase 1 Activity in Crude Biological Samples

Published on: December 2, 2022

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

Related Concept Videos

DNA Topoisomerases02:02

DNA Topoisomerases

Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types.  Type I...
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...
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
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...
Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...