Related Experiment Video

Updated: Aug 10, 2025

Live-Cell Imaging of Transcriptional Activity at DNA Double-Strand Breaks
09:07

Live-Cell Imaging of Transcriptional Activity at DNA Double-Strand Breaks

Published on: September 20, 2021

2.7K

Taspase1 Facilitates Topoisomerase IIβ-Mediated DNA Double-Strand Breaks Driving Estrogen-Induced Transcription

Lisa Oelschläger1, Paul Stahl1, Farnusch Kaschani2

  • 1Department of Molecular Biology II, Center of Medical Biotechnology (ZMB), University Duisburg-Essen, 45141 Essen, Germany.

Cells
|February 11, 2023
PubMed

Insights

The human protease Taspase1 acts as a co-activator for estrogen-stimulated transcription by linking hormone induction to DNA breaks and epigenetic changes. This protease processes key regulators like MLL, impacting development and cancer.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Biology

Background:

  • Taspase1 is a human protease crucial for development and cancer.
  • Its precise biological pathway and signaling cascade remain poorly understood.
  • Taspase1 processes critical regulators like the leukemia proto-oncoprotein MLL.

Purpose of the Study:

  • To elucidate the cellular function and biological pathways of Taspase1.
  • To investigate the role of Taspase1 in hormone-induced transcription.
  • To determine Taspase1's interaction with DNA-modifying enzymes.

Main Methods:

  • Co-immunoprecipitation
  • Liquid chromatography-tandem mass spectrometry (LC-MS/MS)
  • Topoisomerase II DNA cleavage assays
  • siRNA-mediated knockdown

Main Results:

  • Taspase1 functionally links hormone-induced, Topoisomerase IIβ-mediated DNA double-strand breaks to active transcription.
  • Interaction with Topoisomerase IIα enhances DNA double-strand breaks, crucial for stimulus-driven gene transcription.
  • Taspase1 cleaves MLL, altering the H3K4 epigenetic signature upon estrogen stimulation.
  • Taspase1 knockdown reduces estrogen-driven transcription and MLL-derived epigenetic labeling.

Conclusions:

  • Taspase1 is characterized as a multifunctional co-activator of estrogen-stimulated transcription.
  • The study reveals Taspase1's role in mediating DNA breaks and epigenetic modifications.
  • Taspase1's function is directly linked to hormone signaling pathways and gene regulation.
Keywords:
H3K4me3Mixed-lineage leukemiahistone epigenetic labellinghormonesstimulus-triggered transcription

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

2.7K
Dissection of Enhancer Function Using Multiplex CRISPR-based Enhancer Interference in Cell Lines10:46

Dissection of Enhancer Function Using Multiplex CRISPR-based Enhancer Interference in Cell Lines

Published on: June 2, 2018

9.4K

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. ...
31.5K
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
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
12.7K
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...
10.1K
Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
7.1K
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,...
5.9K