コンクエスタドールカジノログイン

This site uses Google Analytics to monitor site usage.Google Analytics uses COOKIEs to collect user information. View our COOKIE policy. Do not acceptAcceptGo To ContentHomeNewsEventsThemesAccessDonateJASearch MenuHomeHomeWho we areWho we areAbout usAbout usAbout usAcademic CalendarMessage from the PresidentQuestionnaireSite PolicyOfficial social media accountsThe UniversityFacts and FiguresVisionVisionVisionOur visionResearch: Working with society, for societyEducation: Thinking globallyInternational: Hub campusLocal Partnerships: Training for the futurePartner UniversitiesInternational OfficesInitiatives for SDGsThe Kobe University FundOur HistoryOur HistoryOur HistoryOur HistoryThe Kobe University FundThe Kobe University FundThe Kobe University FundThe Kobe University FundOrganization and University AdministrationOrganization and University AdministrationOrganization and University AdministrationExecutive membersContactKobe University DirectoryRules and RegulationsChartersChartersChartersCharter on EducationCharter on EnvironmentCharter on ResearchPublic RelationsPublic RelationsPublic RelationsPublic RelationsPublications - Back numbersPress Release ProcedureInformation DisclosureInformation DisclosureInformation DisclosureInternational ProgramsDistinctive Education and Research ProgramsCertified Evaluation and AccreditationLong-term Plan and Evaluation of the UniversityMission and GoalAcademic OrganizationTeaching StaffStudentsCurriculum, Standard for Grading System, Criteria for Graduation Completion of CourseEducation and Research Environments for StudentsTuition and FeesStudent SupportInternational ActivitiesStudying in JapanFor International StudentsUniversity Information and DisclosureCampusCampusCampusCampusStudy in KobeStudy in KobeAdmissionsAdmissionsAdmissionsAbout admissionsAdmission Policy of Kobe UniversityUndergraduate AdmissionsGraduate School Admissions - Master's programmesGraduate School Admissions - Doctoral programmesResearch StudentsExchange programsCourses in EnglishCourses in EnglishCourses in EnglishEnglish-Based Master's Program (MA, Graduate School of Science)ICHS Course (MA, PhD, Graduate School of Health Sciences)International Program for Medical Research (PhD, Graduate School of Medicine)Kobe Global Graduate Program for Agricultural Science (MA, PhD, Graduate School of Agricultural Science)Kobe University Interdisciplinary Master Program (KIMAP)SESAMI PhD Program (PhD, Graduate School of Business Administration)Special Course on Development Policy (MA, Graduate School of International Cooperation)CoursesCoursesCoursesAgricultural Engineering and Socio-Economics (Bachelor)Agricultural Engineering and Socio-Economics (Doctoral)Agricultural Engineering and Socio-Economics (Master)Agrobioscience (Bachelor)Agrobioscience (Doctoral)Agrobioscience (Master)Architecture (Bachelor)Architecture (Doctoral)Architecture (Master)Biology (Bachelor)Biology (Doctoral)Biology (Master)Biomedical Sciences (Master)Bioresource Science (Bachelor)Bioresource Science (Doctoral)Bioresource Science (Master)Business Administration (Bachelor)Business Administration (Doctoral)Business Administration (Master)Chemical Science and Engineering (Bachelor)Chemical Science and Engineering (Doctoral)Chemical Science and Engineering (Master)Chemistry (Bachelor)Chemistry (Doctoral)Chemistry (Master)Child Education (Bachelor)Computational Science (Doctoral)Computational Science (Master)Cultural Interaction (Doctoral)Cultural Interaction (Master)Culture and Globalization (Doctoral)Culture and Globalization (Master)Development and Economics Program (Doctoral)Development and Economics Program (Master)Economics (Bachelor)Economics (Doctoral)Economics (Master)Engineering, Civil (Bachelor)Engineering, Civil (Doctoral)Engineering, Civil (Master)Engineering, Computer and Systems (Bachelor)Engineering, Electrical and Electronic (Bachelor)Engineering, Electrical and Electronic (Doctoral)Engineering, Electrical and Electronic (Master)Engineering, Mechanical (Bacheloar)Engineering, Mechanical (Doctoral)Engineering, Mechanical (Master)Environment and Sustainability (Bachelor)Global Cultures (Bachelor)Global Transportation Sciences (Bachelor)Health Sciences (Bachelor)Health Sciences (Doctoral)Health Sciences (Master)Human Cultural Studies (Doctoral)Human Cultural Studies (Master)Human Development and Community (Bachelor)Human Development (Doctoral)Human Development (Master)Human Environmental Science (Doctoral)Human Environmental Science (Master)Human Social Dynamics (Doctoral)Human Social Dynamics (Master)Humanities (Bachelor)Information Science (Doctoral)Information Science (Master)International Law/Law and Development Program (Doctoral)International Law/Law and Development Program (Master)International Studies Program (Doctoral)International Studies Program (Master)Kobe University Interdisciplinary Master Program (KIMAP)Law (Bachelor)Law and Politics (Law - Master)Law and Politics (Law - Doctoral)Law and Politics (Political Science - Doctoral)Law and Politics (Political Science - Master)Marine Engineering (Bachelor)Maritime Sciences (Doctoral)Maritime Sciences (Master)Mathematics (Bachelor)Mathematics (Doctoral)Mathematics (Master)Medical Sciences (Doctoral)Medicine (Bachelor)Ocean Safety Systems Science (Bachelor)Physics (Bachelor)Physics (Doctoral)Physics (Master)Planetology (Bachelor)Planetology (Doctoral)Planetology (Master)Political Science and Area Studies Program (Doctoral)Political Science and Area Studies Program (Master)Science, Technology and Innovation (Doctoral)Science, Technology and Innovation (Master)Systems Science (Doctoral)Systems Science (Master)Short Term ProgramsShort Term ProgramsShort Term ProgramsShort Term ProgramsAcademic PolicyAcademic PolicyAcademic PolicyDiploma PolicyCurriculum PolicyStudy in JapanStudy in JapanStudy in JapanStudy in JapanProcedures for Entering JapanChange of Status of ResidenceExtension of Period of StayImmigration and Residence Procedures upon Arrival in JapanInviting Family Members to Japan and Necessary Procedures after their ArrivalLeaving Japan temporarily and Re-entryOrientation for New International StudentsWork Permit for Part-time JobsProcedure for Staying in JapanResidence Card ReissuanceInformation to report to the Immigration BureauResidence CardTemporary Withdrawal from UniversityCampus LifeCampus LifeAbout Kobe and HyogoAbout Kobe and HyogoAbout Kobe and HyogoAbout Hyogo PrefectureAbout Kobe CityTop 5 Must-see Attractions in KobeCampus GuideCampus GuideCampus GuideKobe University CafeteriasRegistered Tangible Cultural Properties in Kobe UniversityFacilities for Fitness and Extracurricular ActivitiesKobe University Medical Center for Student HealthInformation Science and Technology CenterKobe University Learning CommonsLearning Facilities and Relaxing EnvironmentsKobe University LibrariesStudent LifeStudent LifeStudent LifeClubs and Circles in Kobe UniversityDaily lifeStudent voicesAcademic CalendarAcademic CalendarAcademic CalendarAcademic CalendarTuition and FeesTuition and FeesTuition and FeesAbout TuitionAbout Enrollment Fee Exemption and DeferralAbout Tuition Fee ExemptionEnrollment Fee Exemption and Deferral Tuition Fee ExemptionStudent SupportStudent SupportStudent SupportStudent SupportHousing InformationHousing InformationHousing InformationHousing InformationKobe University Residential FacilitiesPrivate Dormitories and ResidencesRental Guarantor System at Kobe UniversityWhen moving outPrivate HousingScholarshipsScholarshipsScholarshipsScholarshipsPre-enrollment ScholarshipsCareersCareersCareersCareersInternshipsKobe University Tokyo Office - Career Centre, Tokyo BranchAlumniAlumniAlumniOverseas Alumni AssociationsKobe University Homecoming DayKobe University Community Network "KU-Net"Notice regarding the issuing of various certificates for graduatesResearch andCorporate RelationsResearch andCorporate RelationsResearch SupportResearch SupportResearch SupportResearch SupportAccommodationGrant Application Support in EnglishHandbook for international researchersSupport schemeCode of Conduct for ScientistsFunded Research ProgramsFunded Research ProgramsFunded Research ProgramsFunded Research ProgramsGrants-in-Aid for Scientific ResearchKobe University Strategic International Collaborative Research GrantDevelopment of a global-standard, minimally invasive, functional brain network mapping technique for brain surgeryEstablishing an Asian Network to develop a novel treatment for prostate cancerInternational consortium on ‘Mie-tronics’: a new emerging field of nanophotonicsInternational agricultural research platform for sustainable food productionIlluminating how huge earthquakes occur in Japan, Mexico and ChileCreating an international innovation hub for engineering biologyInternational membrane consortium on research and education strives for sustainable and carbon-neutral societiesInstitute of Promoting Academic Research ProgramsInstitute of Promoting Academic Research ProgramsInstitute of Promoting Academic Research ProgramsInstitute of Promoting Academic Research ProgramsOffice of Research ManagementOrganization for Advanced and Integrated ResearchResearch Facility Center for Science and TechnologyCollaborationCollaborationCollaborationCollaborationEnterprise Partnerships DivisionOffice of Promoting Regional PartnershipFaculties and SchoolsFaculties and SchoolsNewsNewsCategoryFeaturesInterviewsProjectsSpecial issuesPress releasesSDGsGoal 1: No povertyGoal 2: Zero hungerGoal 3: Good health and well-beingGoal 4: Quality educationGoal 5: Gender equalityGoal 6: Clean water and sanitationGoal 7: Affordable and clean energyGoal 8: Decent work and economic growthGoal 9: Industry, Innovation and InfrastructureGoal 10: Reduced inequalityGoal 11: Sustainable cities and communitiesGoal 12: Responsible consumption and productionGoal 13: Climate actionGoal 14: Life below waterGoal 15: Life on landGoal 16: Peace, justice and strong institutionsGoal 17: Partnership for the goalsAreasSocial sciencesMathematics and physicsChemistryEngineering sciencesInformaticsBiological sciencesAgriculture and EnvironmentMedicine, dentistry and pharmacologyHumanitiesEventsEventsEvent categoriesTalksOpen lecturesUniversity activitiesEvent areasSocial sciencesEvent locationsRokkodai 1st CampusOff-campusOnlineEvent audiencesStudentsAudienceProspective studentsCurrent studentsAlumsCorporate and societyFaculty and staff CloseNews TopCategoriesPress releasesRead in日本語2023.06.09New insight into how xeroderma pigmentosum causative gene products ensure the accuracy of DNA repair Medicine, dentistry and pharmacologyRadiation influenceGenetics / Genome scienceDamage/Repair (biology)Xeroderma pigmentosumIntractable diseasesCryo-electron microscopesAn international research group including Professor Kaoru Sugasawa of the Biosignal Research Center, Kobe University, Dr. Fumio Hanaoka, Director-General of the National Institute of Genetics, and Dr. Wei Yang of the National Institutes of Health, USA, has successfully elucidated the elaborate molecular mechanism that ensures the proper repair of DNA damaged by ultra-violet light or chemical carcinogens. This work is expected to deepen our understanding of DNA repair mechanisms that prevent cancer and other diseases. The results of this research were published in Nature at 16:00 UTC on Wednesday, April 19th.Main PointsXPC protein acts as a sensor to detect various abnormalities in the DNA structure.The faithful repair of DNA is ensured by using the basal transcription factor TFIIH and XPA protein to verify the presence of any lesion that needs to be repaired.Using the XPB and XPD proteins present in TFIIH as “motors” to pull the DNA into the protein complex from both directions, the presence of damage is finally verified when the movement of a DNA strand is blocked by the lesion.The present research provides the first explanation of the detailed function and mechanism of xeroderma pigmentosum causative gene products, such as XPA, XPB and XPD, in DNA repair processes.Research BackgroundOur genomic DNA is continuously damaged by endogenous factors such as reactive oxygen species, and also by environmental factors such as ultra-violet light, radiation, and chemicals. Failure to repair damaged DNA may induce mutations and cell death, eventually leading to the onset of cancer and other diseases. To prevent this, our cells are equipped with various defense systems aimed at finding and repairing damaged DNA.Nucleotide excision repair (NER) is an important mechanism for the repair of diverse DNA lesions caused by ultra-violet light and chemical carcinogens. Many patients diagnosed with xeroderma pigmentosum (XP) have mutations in one of the genes encoding proteins involved in the NER mechanism. It is known that their high susceptibility to ultra-violet light induced skin cancer in particular is due to the deficiency in NER function. This also tells us that NER serves as a defense against cancer.The first step of NER involves the XPC protein, one of the several XP causative gene products, which operates as a “sensor” to locate abnormalities in the DNA structure. XPC has a potential to deal with a wide variety of DNA lesions, while it also binds to DNA sites without any damage, such as base mismatches. Since unnecessary repair reactions at such improper sites may increase a risk of adverse mutations, it is essential to verify if there is any damage that needs to be repaired. Although it has previously been shown that the basal transcription factor TFIIH and XPA protein play a role in such a damage verification step, the detailed mechanism has remained unclear up to now.Research MethodologyFollowing the known reaction steps in the NER process, the current researchers prepared a series of complexes containing damaged DNA sequentially bound by XPC, TFIIH and XPA, which were then subjected to cryogenic electron microscopy to analyze their molecular structures in detail. TFIIH is a large protein complex composed of seven subunits, including XPB and XPD proteins, which plays crucial roles in both NER and transcription (gene expression). It usually adopts a U-shaped “horseshoe” structure, with the XPB and XPD proteins positioned at the tips of its two open arms. This horseshoe structure was retained in the DNA-XPC-TFIIH complex, with XPB bound to XPC at the damage site, while XPD does not interact with either DNA or XPC (Figure 1C). When XPA was subsequently involved, however, TFIIH underwent a major conformational change. While the two open arms of the horseshoe came together to form a ring-shaped structure, XPB moved away from the damaged site such that XPD was allowed to bind DNA in between (Figure 1D).Figure 1: The mechanism of DNA damage recognition proposed from this study.Credit: SUGASAWA Kaoru, License:CC BYHow does this molecular arrangement then verify the presence of DNA damage? It is known that XPB functions as a "DNA translocase", which binds to the DNA duplex and move along one of the DNA strands. Based on the newly elucidated structure for the complex, it was assumed that XPB should move along the DNA away from the damage site. However, since it is constrained by other proteins, XPB cannot itself move actually: instead, the DNA duplex moves in the opposite direction. In other words, XPB pushes DNA into the complex (Figure 1E). Because the structure revealed that part of XPA is inserted between the two DNA strands behind XPB, this is expected to unwind the DNA duplex into single strands like a fastener being unzipped. Moreover, it was also known that XPD binds to single-stranded DNA and move along it in a defined direction (5’­→3’). Of the two DNA strands unraveled by XPB and XPA, XPD binds to the damaged one. However, as is the case with XPB, the XPD cannot itself move so the damaged strand is likewise pulled towards the complex (Figure 1E). When bound to a single-stranded DNA, a narrow pinhole is formed in XPD, through which the DNA strand passes. Therefore, if there is a bulky lesion on the DNA strand, that part will be trapped at the entrance to XPD such that the strand will stop its moving (like a knotted thread being unable to pass through the eye of a needle: Figure 1F). The present research thus successfully elucidated the mechanism whereby the presence of a DNA lesion is verified: the decision to proceed with the repair reaction is made by the blockage of DNA strand movement through XPD. In fact, previous researches have indicated that non-bulky DNA lesions (base detachment, etc.) that could be predicted to pass through the XPD hole are not a target for the NER repair process.Further ResearchThe current research has clarified which parts of proteins such as XPA, XPB, and XPD are involved in the NER process to repair damaged DNA together with their mechanism of action. As our understanding deepens about the negative impact on repair response arising from structural changes induced in pathogenic variants of these proteins in XP patients, it may also be possible to support the future development of drugs and other treatments. The fact that Japan in particular has an overwhelmingly high ratio of XP patients with variant XPA, places huge significance on improving our understanding of the relationship between protein structure and function.GlossaryXeroderma pigmentosum (XP)A recessive hereditary disorder in humans characterized by hypersensitivity to sunlight and a high incidence of skin cancer. XP patients have biallelic mutations in one of eight types of causative genes. XPA –XPG proteins, expressed from seven of these genes (XPA – XPG), are directly involved in the nucleotide excision repair (NER). Designated as an intractable disease, at least half the XP patients in Japan are attributed to variant XPA genes.Cryogenic electron microscopyA microscopy method that analyzes biological samples at low temperatures (usually -196ºC, liquid nitrogen), causing much lower electron beam damage to the sample than by conventional transmission electron microscopy. This method allows the observation of high-resolution structure by maintaining the sample condition closer to that within the living organism. Awarded the Nobel Prize in Chemistry in 2017.AcknowledgementsThis study was supported by Grants-in-Aid for Scientific Research (S) (JP16H06307) and (B) (JP21H03598), from the Japan Society for the Promotion of Science.Journal InformationTitle“Lesion recognition by XPC, TFIIH and XPA in DNA excision repair”DOI10.1038/s41586-023-05959-zAuthors: Jinseok Kim, Chia-Lung Li, Xuemin Chen, Yanxiang Cui, Filip M. Golebiowski, Huaibin Wang,Fumio Hanaoka, Kaoru Sugasawa, and Wei YangJournalNatureAccess at the Kobe University Repository KernelResearchersSugasawa KaoruProfessorBiosignal Research CenterBiosignal Research CenterSHAREMore from these researchersPress releases2020.12.08Medicine, dentistry and pharmacologyNew findings shed light on the repair of UV-induced DNA damagePress releases2019.06.20Medicine, dentistry and pharmacologyA new mechanism for accessing damaged DNAPress releases2016.04.27Medicine, dentistry and pharmacologyMechanism revealed for repairing DNA damaged by UV radiationMore about these topicsPress releases2023.03.10Medicine, dentistry and pharmacologyAncient virus genome drives autism?Press releases2022.08.02Medicine, dentistry and pharmacologyImportant insight into cell shape formationPress releases2022.06.01Medicine, dentistry and pharmacologyWorld-first: A biomarker that can diagnose Parkinson’s diseasePress releases2021.07.09Medicine, dentistry and pharmacologyNew genetic driver of autism and other developmental disorders identifiedページの先頭へ1-1, Rokkodai-cho, Nada-ku, Kobe, 657-8501, JAPANProspective studentsCurrent studentsAlumsCorporate and societyFaculty and staffContactAccessJobsOfficial social media accountsCampus calendarPrivacy policySite policySite map© Kobe University