title: Mitotic regulator Nlp interacts with XPA/ERCC1 complexes and regulates nucleotide excision repair (NER) in response to UV radiation.
abstract: Cellular response to DNA damage, including ionizing radiation (IR) and UV radiation, is critical for the maintenance of genomic fidelity. Defects of DNA repair often result in genomic instability and malignant cell transformation. Centrosomal protein Nlp (ninein-like protein) has been characterized as an important cell cycle regulator that is required for proper mitotic progression. In this study, we demonstrate that Nlp is able to improve nucleotide excision repair (NER) activity and protects cells against UV radiation. Upon exposure of cells to UVC, Nlp is translocated into the nucleus. The C-terminus (1030-1382) of Nlp is necessary and sufficient for its nuclear import. Upon UVC radiation, Nlp interacts with XPA and ERCC1, and enhances their association. Interestingly, down-regulated expression of Nlp is found to be associated with human skin cancers, indicating that dysregulated Nlp might be related to the development of human skin cancers. Taken together, this study identifies mitotic protein Nlp as a new and important member of NER pathway and thus provides novel insights into understanding of regulatory machinery involved in NER.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Li
authors.initials: L
authors.lastname: Shang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China. Electronic address: zhanqimin@pumc.edu.cn.
authors.forename: Qi-Min
authors.initials: QM
authors.lastname: Zhan
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000502:physiology*; D004720:Endonucleases / Q000502:physiology*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D009381:Neoplasms, Radiation-Induced / Q000209:etiology; D009687:Nuclear Proteins / Q000502:physiology*; D012878:Skin Neoplasms / Q000209:etiology; D014466:Ultraviolet Rays; D051760:Xeroderma Pigmentosum Group A Protein / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D008869:Microtubule-Associated Proteins; C476755:NINL protein, human; D009687:Nuclear Proteins; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; C071447:ERCC1 protein, human; D004720:Endonucleases
keywords: Genomic stability; NER; Nlp; Tumorigenesis; UV radiation