Sequence-dependent bending of DNA induced by cisplatin: NMR structures of an A.T-rich 14-mer duplex.
The NMR solution structure of the A.T rich DNA 14-mer duplex d(ATACATGGTACATA).d(TATGTACCATGTAT) is reported. This is compared with the NMR structure of the same duplex intrastrand cross-linked at the d(G*pG*) site by cis-(Pt(NH3)2¿2+, derived from the anticancer drug cisplatin. The unmodified duple...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2000
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| _version_ | 1826262788027187200 |
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| author | Parkinson, J Chen, Y del Socorro Murdoch, P Guo, Z Berners-Price, S Brown, T Sadler, P |
| author_facet | Parkinson, J Chen, Y del Socorro Murdoch, P Guo, Z Berners-Price, S Brown, T Sadler, P |
| author_sort | Parkinson, J |
| collection | OXFORD |
| description | The NMR solution structure of the A.T rich DNA 14-mer duplex d(ATACATGGTACATA).d(TATGTACCATGTAT) is reported. This is compared with the NMR structure of the same duplex intrastrand cross-linked at the d(G*pG*) site by cis-(Pt(NH3)2¿2+, derived from the anticancer drug cisplatin. The unmodified duplex has B-DNA geometry, but there is a large positive base-pair roll (roll angle 24 +/- 2 degrees) at the T9-A10 step on the 3' side of the central GG site. Platination of the DNA duplex causes the adjacent guanine bases to roll toward one another (roll angle 44 +/- 4 degrees), leading to an overall helix bend of 52 +/- 9 degrees. The platinum atom is displaced from the planes of the coordinated G7* and G8* by 0.8 A and 0.3 A, respectively. The minor groove opposite the platinum lesion is widened and flattened, with geometric parameters similar to those of A-form DNA. The unwinding of the helix at the platination site is 26 degrees. Platination causes the DNA duplex to bend toward the 3'-end (with respect to the G*G* strand), in contrast to G C-rich structures reported previously, which bend toward the 5'-end. This difference can be attributed to the predisposition of the A.T rich duplex toward bending in this region. Protein recognition of bent platinated G*G* lesions may therefore exhibit a strong dependence on the local DNA structure. |
| first_indexed | 2024-03-06T19:41:37Z |
| format | Journal article |
| id | oxford-uuid:20e07881-4333-400f-b34a-423106f18005 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:41:37Z |
| publishDate | 2000 |
| record_format | dspace |
| spelling | oxford-uuid:20e07881-4333-400f-b34a-423106f180052022-03-26T11:29:58ZSequence-dependent bending of DNA induced by cisplatin: NMR structures of an A.T-rich 14-mer duplex.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:20e07881-4333-400f-b34a-423106f18005EnglishSymplectic Elements at Oxford2000Parkinson, JChen, Ydel Socorro Murdoch, PGuo, ZBerners-Price, SBrown, TSadler, PThe NMR solution structure of the A.T rich DNA 14-mer duplex d(ATACATGGTACATA).d(TATGTACCATGTAT) is reported. This is compared with the NMR structure of the same duplex intrastrand cross-linked at the d(G*pG*) site by cis-(Pt(NH3)2¿2+, derived from the anticancer drug cisplatin. The unmodified duplex has B-DNA geometry, but there is a large positive base-pair roll (roll angle 24 +/- 2 degrees) at the T9-A10 step on the 3' side of the central GG site. Platination of the DNA duplex causes the adjacent guanine bases to roll toward one another (roll angle 44 +/- 4 degrees), leading to an overall helix bend of 52 +/- 9 degrees. The platinum atom is displaced from the planes of the coordinated G7* and G8* by 0.8 A and 0.3 A, respectively. The minor groove opposite the platinum lesion is widened and flattened, with geometric parameters similar to those of A-form DNA. The unwinding of the helix at the platination site is 26 degrees. Platination causes the DNA duplex to bend toward the 3'-end (with respect to the G*G* strand), in contrast to G C-rich structures reported previously, which bend toward the 5'-end. This difference can be attributed to the predisposition of the A.T rich duplex toward bending in this region. Protein recognition of bent platinated G*G* lesions may therefore exhibit a strong dependence on the local DNA structure. |
| spellingShingle | Parkinson, J Chen, Y del Socorro Murdoch, P Guo, Z Berners-Price, S Brown, T Sadler, P Sequence-dependent bending of DNA induced by cisplatin: NMR structures of an A.T-rich 14-mer duplex. |
| title | Sequence-dependent bending of DNA induced by cisplatin: NMR structures of an A.T-rich 14-mer duplex. |
| title_full | Sequence-dependent bending of DNA induced by cisplatin: NMR structures of an A.T-rich 14-mer duplex. |
| title_fullStr | Sequence-dependent bending of DNA induced by cisplatin: NMR structures of an A.T-rich 14-mer duplex. |
| title_full_unstemmed | Sequence-dependent bending of DNA induced by cisplatin: NMR structures of an A.T-rich 14-mer duplex. |
| title_short | Sequence-dependent bending of DNA induced by cisplatin: NMR structures of an A.T-rich 14-mer duplex. |
| title_sort | sequence dependent bending of dna induced by cisplatin nmr structures of an a t rich 14 mer duplex |
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