Forming a chromium-based interstrand DNA crosslink: Implications for carcinogenicity

J Inorg Biochem. 2023 Nov 25;251:112439. doi: 10.1016/j.jinorgbio.2023.112439. Online ahead of print.ABSTRACTThe reduction of the carcinogen chromate has been proposed to lead to three Cr(III)-containing DNA lesions: binary adducts (Cr(III) and DNA), interstrand crosslinks, and ternary adducts (Cr(III) linking DNA to a small molecule or protein). Although the structures of binary adducts have recently been elucidated, the structures of interstrand crosslinks and ternary adducts are not known. Analysis of Cr(III) binding to an oligonucleotide duplex containing a 5'-CG site allows elucidation of the structure of an oxide- or hydroxide-bridged binuclear Cr(III) assembly bridging the two strands of DNA. One Cr(III) is directly coordinated by the N-7 atom of a guanine residue, and the complex straddles the helix to form a hydrogen bond between another guanine residue and a Cr(III)-bound aquo ligand. No involvement of the phosphate backbone was observed. The properties and stability of this Cr-O(H)-Cr-bridged complex differ significantly from those reported for Cr-induced interstrand crosslinks, suggesting that interstrand crosslinks resulting from chromate reduction may be organic in nature.PMID:38039560 | DOI:10.1016/j.jinorgbio.2023.112439

Source: Journal of Inorganic Biochemistry - December 1, 2023 Category: Biochemistry Authors: Silas Brown Sydney Marchi C Sumner Thomas Ashlyn R Hale Molly Lockart Michael K Bowman George Christou Stephen A Woski John B Vincent Source Type: research