Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein Interactions
We showed that XPC complex, which is a DNA damage detector for nucleotide excision repair, stimulates activity of thymine DNA glycosylase (TDG) that initiates base excision repair. XPC appeared to facilitate the enzymatic turnover of TDG by promoting displacement from its own product abasic site, a...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | Journal of Nucleic Acids |
| Online Access: | http://dx.doi.org/10.4061/2010/805698 |
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| author | Yuichiro Shimizu Yasuhiro Uchimura Naoshi Dohmae Hisato Saitoh Fumio Hanaoka Kaoru Sugasawa |
| author_facet | Yuichiro Shimizu Yasuhiro Uchimura Naoshi Dohmae Hisato Saitoh Fumio Hanaoka Kaoru Sugasawa |
| author_sort | Yuichiro Shimizu |
| collection | DOAJ |
| description | We showed that XPC complex, which is a DNA damage detector for nucleotide excision repair, stimulates activity of thymine DNA glycosylase (TDG) that initiates base excision repair. XPC appeared to facilitate the enzymatic turnover of TDG by promoting displacement from its own product abasic site, although the precise mechanism underlying this stimulation has not been clarified. Here we show that XPC has only marginal effects on the activity of E. coli TDG homolog (EcMUG), which remains bound to the abasic site like human TDG but does not significantly interacts with XPC. On the contrary, XPC significantly stimulates the activities of sumoylated TDG and SMUG1, both of which exhibit quite different enzymatic kinetics from unmodified TDG but interact with XPC. These results point to importance of physical interactions for stimulation of DNA glycosylases by XPC and have implications in the molecular mechanisms underlying mutagenesis and carcinogenesis in XP-C patients. |
| format | Article |
| id | doaj-art-dc4fb6dfe1124927a3c374d2a336ce5e |
| institution | Kabale University |
| issn | 2090-021X |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Nucleic Acids |
| spelling | doaj-art-dc4fb6dfe1124927a3c374d2a336ce5e2025-02-03T01:26:28ZengWileyJournal of Nucleic Acids2090-021X2010-01-01201010.4061/2010/805698805698Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein InteractionsYuichiro Shimizu0Yasuhiro Uchimura1Naoshi Dohmae2Hisato Saitoh3Fumio Hanaoka4Kaoru Sugasawa5Cellular Physiology Laboratory, RIKEN Discovery Research Institute, Wako, Saitama 351-0198, JapanDepartment of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, JapanBiomolecular Characterization Team, RIKEN Discovery Research Institute, Wako, Saitama 351-0198, JapanDepartment of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, JapanCellular Physiology Laboratory, RIKEN Discovery Research Institute, Wako, Saitama 351-0198, JapanCellular Physiology Laboratory, RIKEN Discovery Research Institute, Wako, Saitama 351-0198, JapanWe showed that XPC complex, which is a DNA damage detector for nucleotide excision repair, stimulates activity of thymine DNA glycosylase (TDG) that initiates base excision repair. XPC appeared to facilitate the enzymatic turnover of TDG by promoting displacement from its own product abasic site, although the precise mechanism underlying this stimulation has not been clarified. Here we show that XPC has only marginal effects on the activity of E. coli TDG homolog (EcMUG), which remains bound to the abasic site like human TDG but does not significantly interacts with XPC. On the contrary, XPC significantly stimulates the activities of sumoylated TDG and SMUG1, both of which exhibit quite different enzymatic kinetics from unmodified TDG but interact with XPC. These results point to importance of physical interactions for stimulation of DNA glycosylases by XPC and have implications in the molecular mechanisms underlying mutagenesis and carcinogenesis in XP-C patients.http://dx.doi.org/10.4061/2010/805698 |
| spellingShingle | Yuichiro Shimizu Yasuhiro Uchimura Naoshi Dohmae Hisato Saitoh Fumio Hanaoka Kaoru Sugasawa Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein Interactions Journal of Nucleic Acids |
| title | Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein Interactions |
| title_full | Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein Interactions |
| title_fullStr | Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein Interactions |
| title_full_unstemmed | Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein Interactions |
| title_short | Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein Interactions |
| title_sort | stimulation of dna glycosylase activities by xpc protein complex roles of protein protein interactions |
| url | http://dx.doi.org/10.4061/2010/805698 |
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