604 RNA methylation facilitates the repair of UV-induced DNA damage and suppresses photocarcinogenesis

نویسندگان

چکیده

UV-induced DNA damage is repaired by nucleotide excision repair (NER) that corrects bulky helix-distorting lesions across the whole genome and essential for preventing mutagenesis skin cancer. Here we show METTL14 (methyltransferase-like 14), a critical component of m6A RNA methyltransferase complex, promotes through regulating mRNA methylation-mediated translation NER factor DDB2 suppresses tumorigenesis. Ultraviolet irradiation down-regulates protein NBR1-dependent selective autophagy. knockdown decreases abundance. Conversely, overexpression wild-type METTL14, but not its enzymatically inactive mutant, increases methylation transcripts. Adding reverses defect in cells, indicating facilitates translation. Similarly, YTHDF1, an reader promoting modified transcripts, decreased levels. Both YTHDF1 bind to transcript. In mice, skin-specific heterozygous deletion Furthermore, as well down-regulated human mouse tumors chronic UV skin, level associated with level, suggesting tumor-suppressive role UV-associated tumorigenesis association regulation. Taken together, these findings demonstrate target autophagy acts epitranscriptomic mechanism regulate photocarcinogenesis.

برای دانلود باید عضویت طلایی داشته باشید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Metastasis suppressor NM23-H1 promotes repair of UV-induced DNA damage and suppresses UV-induced melanomagenesis.

Reduced expression of the metastasis suppressor NM23-H1 is associated with aggressive forms of multiple cancers. Here, we establish that NM23-H1 (termed H1 isoform in human, M1 in mouse) and two of its attendant enzymatic activities, the 3'-5' exonuclease and nucleoside diphosphate kinase, are novel participants in the cellular response to UV radiation (UVR)-induced DNA damage. NM23-H1 deficien...

متن کامل

Molecular and Cellular Pathobiology Metastasis Suppressor NM23-H1 Promotes Repair of UV-Induced DNA Damage and Suppresses UV-Induced Melanomagenesis

Reduced expression of the metastasis suppressor NM23-H1 is associated with aggressive forms of multiple cancers. Here, we establish that NM23-H1 (termed H1 isoform in human, M1 in mouse) and two of its attendant enzymatic activities, the 30–50 exonuclease and nucleoside diphosphate kinase, are novel participants in the cellular response toUV radiation (UVR)–inducedDNAdamage. NM23-H1 deficiency ...

متن کامل

UV-induced DNA damage and repair: a review.

Increases in ultraviolet radiation at the Earth's surface due to the depletion of the stratospheric ozone layer have recently fuelled interest in the mechanisms of various effects it might have on organisms. DNA is certainly one of the key targets for UV-induced damage in a variety of organisms ranging from bacteria to humans. UV radiation induces two of the most abundant mutagenic and cytotoxi...

متن کامل

Hereditary Disorders with Defective Repair of UV-Induced DNA Damage

Nucleotide excision repair (NER) is an essential system for correcting ultraviolet (UV)-induced DNA damage. Lesions remaining in DNA due to reduced capacity of NER may result in cellular death, premature aging, mutagenesis and carcinogenesis of the skin. So, NER is an important protection against these changes. There are three representative genodermatoses resulting from genetic defects in NER:...

متن کامل

UV damage, DNA repair and skin carcinogenesis.

Skin cancer is unique among human cancers in its etiology, accessibility and the volume of detailed knowledge now assembled concerning its molecular mechanisms of origin. The major carcinogenic agent for most skin cancers is well established as solar ultraviolet light. This is absorbed in DNA with the formation of UV-specific dipyrimidine photoproducts. These can be repaired by nucleotide excis...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

ژورنال

عنوان ژورنال: Journal of Investigative Dermatology

سال: 2022

ISSN: ['1523-1747', '0022-202X']

DOI: https://doi.org/10.1016/j.jid.2022.05.614