title: DNA damage induces nuclear translocation of parkin.
abstract: Parkinson's disease (PD) is the second most common form of human degenerative disorder. Mutation of parkin is one of the most prevalent causes of autosomal recessive PD. Parkin is an E3 ubiquitin ligase that acts on a variety of substrates, resulting in polyubiquitination and degradation by the proteasome or monoubiquitination and regulation of biological activity. However, the cellular functions of parkin that relate to its pathological involvement in PD are not well understood. Here I show that parkin translocates into nucleus upon DNA damage. Nuclear translocation of parkin appears to be required to promote DNA repair. These findings suggest that DNA damage induces nuclear translocation of parkin leading to the PCNA interaction and possibly other nuclear proteins involved in DNA repair. These results suggest that parkin promotes DNA repair and protects against genotoxicity, and implicate DNA damage as a potential pathogenic mechanism in parkinsonism.
authors.affiliation: Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston MA 02114, USA. shyan-yuan_kao@meei.harvard.edu
authors.forename: Shyan-Yuan
authors.initials: SY
authors.lastname: Kao
mesh_terms: D021581:Active Transport, Cell Nucleus; D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008954:Models, Biological; D025801:Ubiquitin / Q000737:chemistry; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis*; D014466:Ultraviolet Rays
chemical_list: D025801:Ubiquitin; D004247:DNA; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein