Related Experiment Video
Updated: Jul 6, 2025
09:14
Examination of Proteins Bound to Nascent DNA in Mammalian Cells Using BrdU-ChIP-Slot-Western Technique
Published on: January 14, 2016
9.2K
The m6A reader YTHDC2 regulates UVB-induced DNA damage repair and histone modification
Zizhao Yang1, Michelle Verghese1,2, Seungwon Yang1
1Department of Medicine, Section of Dermatology, University of Chicago, Chicago, Illinois, USA.
Photochemistry and Photobiology
|January 8, 2024
Summary
Inhibiting the m6A reader YTHDC2 enhances DNA repair after UVB damage, suggesting it may promote skin cancer. YTHDC2 upregulation in cutaneous squamous cell carcinoma indicates its potential as a biomarker.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- Ultraviolet B (UVB) radiation is a primary cause of skin cancer, inducing DNA damage like cyclobutane pyrimidine dimers (CPDs).
- Efficient DNA repair, particularly nucleotide excision repair (NER), is crucial for preventing skin carcinogenesis.
- m6A RNA methylation and its regulatory proteins are increasingly recognized for their roles in DNA damage response, but the function of YTHDC2 remains unclear.
Purpose of the Study:
- To investigate the role of the m6A reader YTHDC2 in the repair of UVB-induced DNA damage.
- To explore the potential of YTHDC2 as a biomarker in cutaneous squamous cell carcinoma (cSCC).
Main Methods:
- Investigated the effect of YTHDC2 inhibition on UVB-induced DNA damage repair in skin cells.
- Analyzed the expression of PTEN, SUZ12, and H3K27me3 following YTHDC2 inhibition.
- Examined the impact of METTL14 and FTO modulation on DNA repair in conjunction with YTHDC2 inhibition.
- Compared YTHDC2 expression levels in normal human skin versus human cutaneous squamous cell carcinomas (cSCC).
Main Results:
- YTHDC2 inhibition significantly enhanced the repair of UVB-induced DNA damage.
- YTHDC2 inhibition altered the expression of PTEN and SUZ12, and H3K27me3 levels, though not causally linked to improved DNA repair.
- Modulation of m6A writers (METTL14) and erasers (FTO) affected DNA repair, supporting YTHDC2's role in the m6A pathway.
- YTHDC2 expression was found to be upregulated in human cSCC compared to normal skin.
Conclusions:
- The m6A reader YTHDC2 plays a significant role in regulating the repair of UVB-induced DNA damage.
- YTHDC2 may function as a tumor-promoting factor in skin cancer, particularly in cSCC.
- YTHDC2 represents a potential diagnostic biomarker for cSCC.
Related Concept Videos
02:25Spreading of Chromatin Modifications
8.3K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.3K
02:32Histone Modification
13.3K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.3K
01:38Nucleotide Excision Repair
3.5K
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...
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...
3.5K
01:35Mutations
37.7K
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...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
37.7K
02:04Covalently Linked Protein Regulators
6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
02:30Histone Variants at the Centromere
4.3K
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
4.3K