title: SUMOylation of xeroderma pigmentosum group C protein regulates DNA damage recognition during nucleotide excision repair.
abstract: The xeroderma pigmentosum group C (XPC) protein complex is a key factor that detects DNA damage and initiates nucleotide excision repair (NER) in mammalian cells. Although biochemical and structural studies have elucidated the interaction of XPC with damaged DNA, the mechanism of its regulation in vivo remains to be understood in more details. Here, we show that the XPC protein undergoes modification by small ubiquitin-related modifier (SUMO) proteins and the lack of this modification compromises the repair of UV-induced DNA photolesions. In the absence of SUMOylation, XPC is normally recruited to the sites with photolesions, but then immobilized profoundly by the UV-damaged DNA-binding protein (UV-DDB) complex. Since the absence of UV-DDB alleviates the NER defect caused by impaired SUMOylation of XPC, we propose that this modification is critical for functional interactions of XPC with UV-DDB, which facilitate the efficient damage handover between the two damage recognition factors and subsequent initiation of NER.
authors.affiliation: Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, Kobe 657-8501, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Akita
authors.affiliation: Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, Kobe 657-8501, Japan.
authors.forename: Yon-Soo
authors.initials: YS
authors.lastname: Tak
authors.affiliation: Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, Kobe 657-8501, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shimura
authors.affiliation: 1] Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, Kobe 657-8501, Japan [2] Graduate School of Science, Kobe University, Kobe 657-8501, Japan.
authors.forename: Syota
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Cellular Physiology Laboratory, RIKEN, Wako 351-0198, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Okuda-Shimizu
authors.affiliation: Cellular Physiology Laboratory, RIKEN, Wako 351-0198, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: 1] Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, Kobe 657-8501, Japan [2] Cellular Physiology Laboratory, RIKEN, Wako 351-0198, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Nishi
authors.affiliation: Graduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan.
authors.forename: Hisato
authors.initials: H
authors.lastname: Saitoh
authors.affiliation: Graduate School of Engineering Science, Osaka University, Toyonaka 560-8531, Japan.
authors.forename: Shigenori
authors.initials: S
authors.lastname: Iwai
authors.affiliation: Radioisotope Research Center, Nara Medical University, Kashihara 634-8521, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Mori
authors.affiliation: Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ikura
authors.affiliation: 1] Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, Kobe 657-8501, Japan [2] Graduate School of Science, Kobe University, Kobe 657-8501, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Sakai
authors.affiliation: 1] Cellular Physiology Laboratory, RIKEN, Wako 351-0198, Japan [2] Faculty of Science, Gakushuin University, Tokyo 171-8588, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Hanaoka
authors.affiliation: 1] Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, Kobe 657-8501, Japan [2] Graduate School of Science, Kobe University, Kobe 657-8501, Japan [3] Cellular Physiology Laboratory, RIKEN, Wako 351-0198, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sugasawa
mesh_terms: D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D011485:Protein Binding; D025842:SUMO-1 Protein / Q000378:metabolism; D058207:Sumoylation; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D054875:Ubiquitination / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D025842:SUMO-1 Protein; C086984:XPC protein, human; D044763:Ubiquitin-Conjugating Enzymes