Related Experiment Video

Updated: Jun 17, 2026

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
04:12

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)

Published on: December 19, 2019

Error-prone translesion replication of damaged DNA suppresses skin carcinogenesis by controlling inflammatory

Anastasia Tsaalbi-Shtylik1, Johan W A Verspuy, Jacob G Jansen

  • 1Department of Toxicogenetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.

Proceedings of the National Academy of Sciences of the United States of America
|December 17, 2009
PubMed

Insights

Error-prone translesion synthesis (TLS) normally suppresses skin cancer promotion by UV light. Defects in TLS accelerate skin cancer by inducing inflammatory hyperplasia, revealing a novel role in controlling carcinogenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Skin cancer (carcinogenesis) involves DNA damage from UV light, leading to mutations and proliferation.
  • Translesion synthesis (TLS) pathways are crucial for replicating damaged DNA during tumor initiation.
  • The role of TLS in promoting skin cancer proliferation is not well understood.

Purpose of the Study:

  • To investigate the role of TLS in skin cancer initiation and promotion.
  • To examine the impact of a defective TLS gene (Rev1) on UV-induced skin carcinogenesis.

Main Methods:

  • Utilized a nucleotide excision repair-deficient mouse model with a hypomorphic Rev1 allele.
  • Assessed UV-induced mutagenesis, skin carcinogenesis, inflammatory hyperplasia, and cytokine expression (IL-6).

Main Results:

  • Mice with defective TLS (Rev1) showed accelerated skin carcinogenesis despite reduced UV-induced mutagenesis.
  • This acceleration was due to UV-induced inflammatory hyperplasia, acting as a tumor promoter.
  • Hyperplasia was linked to replicational stress, DNA damage signaling, senescence, and Interleukin-6 (IL-6) expression.

Conclusions:

  • Error-prone TLS suppresses tumor-promoting inflammatory responses to UV light.
  • TLS plays a critical role in controlling skin carcinogenesis by mitigating hyperplasia and promoting senescence.
  • IL-6 is implicated in the induction of senescence and inflammatory hyperplasia, highlighting its role in UV carcinogenesis.

More Related Videos

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

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
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...