Xeroderma pigmentosum group C sensor: unprecedented recognition strategy and tight spatiotemporal regulation
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- 作者：Marjo-Riitta Puumalainen ; Peter Rüthemann…
- 关键词：Aging ; Diurnal life ; DNA repair ; Genomic instability ; Skin cancer ; SUMO ; Sunburn ; Tumor suppressor ; Ubiquitin
- 刊名：Cellular and Molecular Life Sciences (CMLS)
- 出版年：2016
- 出版时间：February 2016
- 年：2016
- 卷：73
- 期：3
- 页码：547-566
- 全文大小：7,973 KB
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Peter Rüthemann (1)
Jun-Hyun Min (3)
Hanspeter Naegeli (1)
1. Institute of Pharmacology and Toxicology, University of Zürich-Vetsuisse, 8057, Zurich, Switzerland
2. Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
3. Department of Chemistry, University of Illinois at Chicago, Chicago, IL, 60607, USA - 刊物类别：Biomedical and Life Sciences
- 刊物主题：Life Sciences
Cell Biology
Biomedicine
Life Sciences
Biochemistry - 出版者：Birkh盲user Basel
- ISSN：1420-9071
文摘
The cellular defense system known as global-genome nucleotide excision repair (GG-NER) safeguards genome stability by eliminating a plethora of structurally unrelated DNA adducts inflicted by chemical carcinogens, ultraviolet (UV) radiation or endogenous metabolic by-products. Xeroderma pigmentosum group C (XPC) protein provides the promiscuous damage sensor that initiates this versatile NER reaction through the sequential recruitment of DNA helicases and endonucleases, which in turn recognize and excise insulting base adducts. As a DNA damage sensor, XPC protein is very unique in that it (a) displays an extremely wide substrate range, (b) localizes DNA lesions by an entirely indirect readout strategy, (c) recruits not only NER factors but also multiple repair players, (d) interacts avidly with undamaged DNA, (e) also interrogates nucleosome-wrapped DNA irrespective of chromatin compaction and (f) additionally functions beyond repair as a co-activator of RNA polymerase II-mediated transcription. Many recent reports highlighted the complexity of a post-translational circuit that uses polypeptide modifiers to regulate the spatiotemporal activity of this multiuse sensor during the UV damage response in human skin. A newly emerging concept is that stringent regulation of the diverse XPC functions is needed to prioritize DNA repair while avoiding the futile processing of undamaged genes or silent genomic sequences. Keywords Aging Diurnal life DNA repair Genomic instability Skin cancer SUMO Sunburn Tumor suppressor Ubiquitin