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Structures of Silver Fingers and a Pathway to Their Genotoxicity

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Kluska, Katarzyna | Veronesi, Giulia | Deniaud, Aurélien | Hajdu, Bálint | Gyurcsik, Béla | Bal, Wojciech | Krężel, Artur

Edité par CCSD ; Wiley-VCH Verlag -

International audience. Recently, we demonstrated that Ag-I can directly replace Zn-II in zinc fingers (ZFs). The cooperative binding of Ag-I to ZFs leads to a thermodynamically irreversible formation of silver clusters destroying the native ZF structure. Thus, a reported loss of biological function of ZF proteins is a likely consequence of such replacement. Here, we report an X-ray absorption spectroscopy (XAS) study of AgnSn clusters formed in ZFs to probe their structural features. Selective probing of the local environment around Ag-I by XAS showed the predominance of digonal Ag-I coordination to two sulfur donors, coordinated with an average Ag-S distance at 2.41 angstrom. No Ag-N bonds were present. A mixed AgS2/AgS3 geometry was found solely in the CCCH Ag-I-ZF. We also show that cooperative replacement of Zn-II ions with the studied Ag2S2 clusters occurred in a three-ZF transcription factor protein 1MEY#, leading to a dissociation of 1MEY# from the complex with its cognate DNA.

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