| MECHANISM OF ACTION |
Inside a cell, cisplatin undergoes hy
drolysis, producing the highly reactive charged Pt complex {Pt(NH3)2
ClH2O}+. This complex coordinates to DNA through the N7 atom of either a
guanine or adenine base. Further hydro
lysis displaces the remaining chloride ligand, & the Pt can bind to a second nucleotide base. The cisplatin-DNA adduct is recognized by a high mobility group (HMG)-domain protein - among other DNA repair proteins - which binds tightly to the complex. The adduct causes destacking of the nucleotide bases, resulting in the DNA helix becoming kinked. In this way, cisplatin can be thought of as a monkey wrench in the DNA excision repair system.
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