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Targeting Abasic Sites and Single Base Bulges in DNA with Metalloinsertors

Zeglis, Brian M. and Boland, Jennifer A. and Barton, Jacqueline K. (2008) Targeting Abasic Sites and Single Base Bulges in DNA with Metalloinsertors. Journal of the American Chemical Society, 130 (24). pp. 7530-7531. ISSN 0002-7863. PMCID PMC2759749. doi:10.1021/ja801479y. https://resolver.caltech.edu/CaltechAUTHORS:20160226-135927342

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Abstract

The site-specific recognition of abasic sites and single base bulges in duplex DNA by sterically expansive rhodium metalloinsertors has been investigated. Through DNA photocleavage experiments, Rh(bpy)_2(chrysi)^(3+) is shown to bind both abasic sites and single base bulges site-specifically and, upon irradiation, to cleave the backbone of the defect-containing DNA. Photocleavage titrations reveal that the metal complex binds DNA containing an abasic site with high affinity (2.6(5) × 10^6 M^(−1)), comparably to the metalloinsertor and a CC mismatch. The complex binds single base bulge sites with lower affinity (∼10^5 M^(−1)). Analysis of cleavage products and the correlation of affinities with helix destabilization suggest that Rh(bpy)_2(chrysi)^(3+) binds both lesions via metalloinsertion, as observed for Rh binding at mismatched sites, a binding mode in which the mismatched or unpaired bases are extruded from the helix and replaced in the base stack by the sterically expansive ligand of the metalloinsertor.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja801479yDOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja801479yPublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/ja801479yPublisherSupporting Information
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759749/PubMed CentralArticle
ORCID:
AuthorORCID
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 2008 American Chemical Society. Received February 27, 2008. Publication Date (Web): May 21, 2008. We are grateful to the NIH (GM33309) for their financial support, the SURF program for a summer internship for J.A.B, and the NSF for a graduate fellowship to B.M.Z.
Funders:
Funding AgencyGrant Number
NIHGM33309
Caltech Summer Undergraduate Research Fellowship (SURF)UNSPECIFIED
NSF Graduate Research FellowshipUNSPECIFIED
Issue or Number:24
PubMed Central ID:PMC2759749
DOI:10.1021/ja801479y
Record Number:CaltechAUTHORS:20160226-135927342
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160226-135927342
Official Citation:Targeting Abasic Sites and Single Base Bulges in DNA with Metalloinsertors Brian M. Zeglis, Jennifer A. Boland, and Jacqueline K. Barton Journal of the American Chemical Society 2008 130 (24), 7530-7531 DOI: 10.1021/ja801479y
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64811
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:29 Feb 2016 18:43
Last Modified:10 Nov 2021 23:35

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