Autophagic UVRAG Promotes UV-Induced Photolesion Repair by Activation of the CRL4(DDB2) E3 Ligase
| Autor: | Nyam Osor Chimge, Baruch Frenkel, Fan Li, Younho Choi, Chengyu Liang, Yongfei Yang, Sara Dolatshahi Pirooz, Tian Zhang, Qiaoxiu Wang, Sally B Chen, Zengqiang Yuan, Douglas O’Connell, Mi Jeong Kwak, Byung-Ha Oh, Shanshan He, Yong Heui Jeon, Grace M. Aldrovandi |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Skin Neoplasms Time Factors DNA Repair Melanoma Experimental Medical and Health Sciences Drosophila Proteins Melanoma Biological Sciences Cullin Proteins Ubiquitin ligase DNA-Binding Proteins Drosophila melanogaster Ubiquitin ligase complex RNA Interference Signal Transduction Xeroderma pigmentosum DNA repair Ultraviolet Rays Ubiquitin-Protein Ligases UVRAG Biology Transfection Retina Article Experimental 03 medical and health sciences DDB1 medicine Autophagy Animals Humans Molecular Biology Tumor Suppressor Proteins Ubiquitination Cell Biology medicine.disease Enzyme Activation 030104 developmental biology HEK293 Cells Hela Cells Proteolysis biology.protein Cancer research Carrier Proteins Developmental Biology Nucleotide excision repair DNA Damage HeLa Cells Transcription Factors |
| Zdroj: | Molecular cell, vol 62, iss 4 Yang, Y; He, S; Wang, Q; Li, F; Kwak, M-J; Chen, S; et al.(2016). Autophagic UVRAG Promotes UV-Induced Photolesion Repair by Activation of the CRL4(DDB2) E3 Ligase. MOLECULAR CELL, 62(4), 507-519. doi: 10.1016/j.molcel.2016.04.014. UCLA: Retrieved from: http://www.escholarship.org/uc/item/1rf7p1n7 |
| ISSN: | 1097-4164 |
| Popis: | Ultraviolet (UV)-induced DNA damage, a major risk factor for skin cancers, is primarily repaired by nucleotide excision repair (NER). UV-radiation Resistance Associated Gene (UVRAG) is a tumor suppressor involved in autophagy. It was initially isolated as a cDNA partially complementing UV sensitivity in Xeroderma Pigmentosum (XP), but this was not explored further. Here we show that UVRAG plays an integral role in UV-induced DNA damage repair. It localizes to photolesions and associates with DDB1 to promote the assembly and activity of the DDB2-DDB1-Cul4A–Roc1 (CRL4DDB2) ubiquitin-ligase complex, leading to efficient XPC recruitment and global-genomic NER. UVRAG depletion decreased substrate handover to XPC and conferred UV-damage hypersensitivity. We confirmed the importance of UVRAG for UV-damage tolerance using a Drosophila model. Furthermore, increased UV-signature mutations in melanoma correlate with reduced expression of UVRAG. Our results identify UVRAG as a regulator of CRL4DDB2-mediated NER and suggest that its expression levels may influence melanoma predisposition. |
| Databáze: | OpenAIRE |
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