Related Experiment Video

Updated: Aug 16, 2025

Visualization of DNA Repair Proteins Interaction by Immunofluorescence
07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

10.3K

TRIM24 is critical for the cellular response to DNA double-strand breaks through regulating the recruitment of MRN

Ya Wang1,2,3, Yuanbing Yao1,4,5, Qunhui Wei2

  • 1Institute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine, Department of General Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.

Oncogene
|December 22, 2022
PubMed

Insights

Tripartite motif-containing protein 24 (TRIM24) is a novel signaling molecule essential for DNA double-strand break (DSB) repair by regulating the MRN complex. TRIM24 depletion sensitizes cancer cells to therapy and retards tumor growth, suggesting its potential as a therapeutic target.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • DNA Repair Mechanisms

Background:

  • The MRE11-RAD50-NBS1 (MRN) complex is critical for sensing DNA double-strand breaks (DSBs) and initiating cellular responses.
  • The exact mechanisms controlling MRN complex recruitment to DSB sites remain unclear.

Purpose of the Study:

  • To identify novel regulators of MRN complex recruitment and function in response to DNA double-strand breaks.
  • To investigate the role of Tripartite motif-containing protein 24 (TRIM24) in DNA damage response pathways.

Main Methods:

  • Identification of TRIM24 as a novel DSB-responsive protein.
  • Assessment of TRIM24's role in MRN complex recruitment and DNA repair.
  • Investigation of TRIM24 phosphorylation by ATM kinase.
  • Evaluation of TRIM24 depletion effects on hepatocellular carcinoma cells and tumor growth in vivo.

Main Results:

  • TRIM24 acts as a signaling molecule essential for DSB-induced MRN complex recruitment and activation of downstream signaling.
  • TRIM24 is phosphorylated by ATM and subsequently recruited to DSB sites, promoting MRN accumulation.
  • Absence of TRIM24 significantly impairs MRN-mediated DSB repair.
  • TRIM24 depletion sensitizes hepatocellular carcinoma cells to apoptosis and inhibits tumor growth in xenograft models.

Conclusions:

  • TRIM24 plays a crucial role in DNA double-strand break repair by regulating the MRN complex.
  • TRIM24's function in DSB response highlights its potential as a therapeutic target for cancer treatment.

More Related Videos

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage10:44

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage

Published on: January 31, 2018

10.3K
Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy08:31

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy

Published on: June 8, 2018

9.2K

Related Concept Videos

Homologous Recombination02:31

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
50.8K
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...
9.3K
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
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
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...
3.7K
Mismatch Repair01:36

Mismatch Repair

Overview
40.5K