Related Experiment Video
Updated: Jun 8, 2026
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Sun-induced nonsynonymous p53 mutations are extensively accumulated and tolerated in normal appearing human skin
Patrik L Ståhl1, Henrik Stranneheim, Anna Asplund
1Division of Gene Technology, Science for Life Laboratory, Royal Institute of Technology, Stockholm, Sweden.
Abstract:
Here we demonstrate that intermittently sun-exposed human skin contains an extensive number of phenotypically intact cell compartments bearing missense and nonsense mutations in the p53 tumor suppressor gene. Deep sequencing of sun-exposed and shielded microdissected skin from mid-life individuals revealed that persistent p53 mutations had accumulated in 14% of all epidermal cells, with no apparent signs of a growth advantage of the affected cell compartments. Furthermore, 6% of the mutated epidermal cells encoded a truncated protein. The abundance of these events, not taking into account intron mutations and mutations in other genes that also may have functional implications, suggests an extensive tolerance of human cells to severe genetic alterations caused by UV light, with an estimated annual rate of accumulation of ∼35,000 new persistent protein-altering p53 mutations in sun-exposed skin of a human individual.
Insights
Sun-exposed skin accumulates numerous p53 gene mutations in epidermal cells, even without causing cell overgrowth. Human skin tolerates significant UV-induced genetic damage, with thousands of new mutations annually.
Area of Science:
- Molecular Biology
- Dermatology
- Genetics
Background:
- The p53 tumor suppressor gene is crucial for preventing cancer.
- UV radiation from sun exposure is a known mutagenic agent.
- Understanding genetic damage in skin cells is vital for cancer prevention.
Purpose of the Study:
- To quantify the accumulation of p53 mutations in sun-exposed human skin.
- To assess the impact of UV radiation on epidermal cell genetics.
- To determine the tolerance of human skin cells to genetic alterations.
Main Methods:
- Deep sequencing was employed on microdissected skin samples.
- Sun-exposed and shielded skin from mid-life individuals were analyzed.
- Phenotypically intact cell compartments were examined for p53 mutations.
Main Results:
- Persistent p53 mutations were found in 14% of all epidermal cells in sun-exposed skin.
- No growth advantage was observed in mutated cell compartments.
- 6% of mutated cells encoded truncated p53 proteins, with an estimated 35,000 new mutations annually.
Conclusions:
- Human skin exhibits significant tolerance to UV-induced genetic damage.
- Extensive accumulation of p53 mutations occurs in sun-exposed skin.
- UV radiation causes substantial protein-altering genetic alterations in epidermal cells.
More Related Videos
Related Concept Videos
01:35Mutations
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
01:39Mutations
01:38Nucleotide Excision Repair
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...
01:08Nucleotide Excision Repair
02:23Abnormal Proliferation
01:19Pigmentation
Melanin occurs in two primary forms: eumelanin that provides black and brown pigment and pheomelanin that provides red color. Dark-skinned individuals produce more melanin than those with pale...