서지주요정보
Structural studies of the photochemically damaged nucleic acid by NMR and molecular modeling = NMR과 분자 모델링에 의한 광손상된 핵산의 구조 연구
서명 / 저자 Structural studies of the photochemically damaged nucleic acid by NMR and molecular modeling = NMR과 분자 모델링에 의한 광손상된 핵산의 구조 연구 / Geum-Sook Hwang.
저자명 Hwang, Geum-Sook ; 황금숙
발행사항 [대전 : 한국과학기술원, 1996].
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소장정보

등록번호

8006887

소장위치/청구기호

학술문화관(문화관) 보존서고

DCH 96022

SMS전송

도서상태

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초록정보

Structural studies of the DNA duplex containing a site specific-photodamaged photoproduct is an essential step toward understanding the molecular mechanism of the mutagenesis and the repair activity of ultraviolet irradiated DNA. The solution structures of two photodamaged DNA, psoralen cross-linked octamer duplex and (6-4) adduct- and Dewar photoproduct- containing decamer duplex, have been elucidated by detailed NMR and molecular modeling. (1) The three dimensional structure of the DNA oligomer $d(5'-GGGTACCC-3')_2$ cross-linked with 4'-aminomethyl-4,5',8-trimethylpsoralen(AMT) has been determined by two-dimensional NMR and a relaxation matrix refinement method. NMR data and structural calculation establish that the cross-linking of the psoralen in the B-DNA duplex retains Watson-Crick type hydrogen bonding throughout the duplex although the thymine residue which is cross-linked with psoralen forms a weaker hydrogen bond. The psoralen cross-linking in DNA duplex induces significant change of the local DNA structure, but has no important effect on overall DNA helix. Our observation places an upper limit of 10° on overall DNA bending by psoralen cross-linking, which is consistent with the result of HMT-octamer cross link. (2) The relative biological importance of (6-4) adduct and Dewar photoproduct appears to be dependent on the biological species, dipyrimidine sites, and the local conformational variation induced at the damaged sites. The single- stranded deoxynucleotide 10-mers containing site-specific (6-4) adduct or Dewar photoproduct of thymidylyl (3→5)-thymidine were generated by direct photolysis of d(CGCATTACGC) with UV-C(220-260nm) and UV-B(260-320nm) irradiation. Three-dimensional structures of the duplex Dewar and (6-4) decamers of d(CGCATTACGC)(d(GCGTAATGCG) were determined by NMR spectroscopy and relaxation matrix refinement method. NMR data and structural calculation establish that the hydrogen bonding is absent at the 3'-side of the (6-4) lesion where the T→C transition mutation is predominantly targeted, while the 5'-TpT-3' bases of the Dewar lesion show no evidence of complementary hydrogen bonding formation to each other resulting in a lower error frequency and broader range of mutations. The detailed NMR data show that the base pairing and stacking of the Dewar decamer duplex differ from that of the (6-4) decamer duplex. Overall conformation of the decamer duplex containing Dewar photoproduct produced a 21°-degree-helical bending in DNA helix, while the decamer duplex containing (6-4) adduct provided a structural basis leading to 44°-degree-helical bending. Contrasting structural distortions induced by the T-T (6-4) adduct with respect to by the Dewar photoproduct may explain the large differences in mutation spectrum and repair activities between them.

서지기타정보

서지기타정보
청구기호 {DCH 96022
형태사항 xvii, 217 p. : 삽도 ; 26 cm
언어 영어
일반주기 Includes appendix
저자명의 한글표기 : 황금숙
지도교수의 영문표기 : Byong-Seok Choi
지도교수의 한글표기 : 최병석
수록 잡지명 : "NMR structural studies of DNA decamer duplex containing the Dewar photoproduct of thymidylyl(3'->5')thymidine". European Journal of Biochemistry. Springer-Verlag, vol. 235, pp. 359-365
학위논문 학위논문(박사) - 한국과학기술원 : 화학과,
서지주기 Reference : p. 153-161
주제 NMR
Molecular modeling
Photochemically damaged
Nucleic acid
Structural analysis
핵자기 공명법
분자 모델링
광손상
핵산
구조 분석
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