Related Experiment Video

Updated: Feb 17, 2026

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay
13:10

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay

Published on: June 9, 2017

10.7K

A20/TNFAIP3 Regulates the DNA Damage Response and Mediates Tumor Cell Resistance to DNA-Damaging Therapy

Chuanzhen Yang1,2, Weicheng Zang1,2, Zefang Tang3

  • 1State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.

Cancer Research
|December 14, 2017
PubMed

Insights

The ubiquitin-editing enzyme A20 inhibits DNA repair, promoting cancer cell resistance to chemotherapy. Blocking A20 may enhance cancer treatment efficacy by improving DNA damage response.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • A functional DNA damage response (DDR) is crucial for preventing cancer.
  • However, in established cancers, DDR can reduce the effectiveness of DNA-damaging therapies like chemotherapy and radiotherapy.
  • Targeting DDR pathways presents a strategy to enhance anticancer treatment outcomes.

Purpose of the Study:

  • To investigate a novel DDR mechanism involving the ubiquitin-editing enzyme A20/TNFAIP3.
  • To determine if blocking this A20-mediated pathway can improve anticancer therapy efficacy.
  • To establish the link between A20, DDR, and inflammatory signaling in cancer.

Main Methods:

  • Investigated the interaction between A20 and the E3 ubiquitin ligase RNF168.
  • Assessed the role of A20 in regulating histone H2A turnover and DNA repair protein localization (RNF168, 53BP1) after DNA damage.
  • Utilized A20 deletion models to evaluate effects on DNA repair pathways (NHEJ, HR) and DNA damage sensitivity.
  • Analyzed A20 expression in clinical breast carcinoma specimens.

Main Results:

  • A20 directly binds and inhibits RNF168, a key regulator of histone H2A turnover for DNA repair.
  • A20 disrupts the RNF168-H2A interaction and inhibits RNF168/53BP1 accumulation at DNA damage sites.
  • A20 is essential for the disassembly of RNF168 and 53BP1 post-repair.
  • A20 deficiency enhances error-prone DNA repair (NHEJ), destabilizes the genome, and increases sensitivity to DNA damage.
  • A20 is overexpressed in invasive breast carcinoma, suggesting its therapeutic potential.

Conclusions:

  • A20 plays a critical role in the DNA damage response within cancer cells.
  • A20 establishes a novel connection between NFκB-regulated inflammatory signaling and the DDR pathway.
  • A20 functions as a mediator of cancer cell resistance to DNA-damaging therapies, making it a potential therapeutic target.

More Related Videos

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells05:18

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells

Published on: June 9, 2020

11.8K
Cell Cycle-specific Measurement of γH2AX and Apoptosis After Genotoxic Stress by Flow Cytometry08:21

Cell Cycle-specific Measurement of γH2AX and Apoptosis After Genotoxic Stress by Flow Cytometry

Published on: September 1, 2019

14.2K

Related Concept Videos

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...
10.2K
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...
3.2K
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...
5.3K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.8K
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.
38.6K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.7K