HMG1 PROTEIN INHIBITS THE TRANSLESION SYNTHESIS OF THE MAJOR DNA CISPLATIN ADDUCT BY CELL-EXTRACTS

When situated in a fork-like synthetic DNA replication substrate, the 1,2-intrastrand crosslink at the d(GpG) site, the most frequent adduct formed in the reaction between DNA and the anticancer drug cisplatin (cis-diamminedichloroplatinum (II)), is efficiently bypassed by eukary otic cell extracts. We show here that the rat high-mobility-group prot ein 1 (HMG1) binds preferentially to the platinated fork-like syntheti c DNA and inhibits the translesion synthesis. The same protein, but wi thout the acidic tail, inhibits also the translesion synthesis. These results suggest that HMG proteins might contribute to the sensitivity of cells to cisplatin by directly affecting DNA replication. (C) 1997 Academic Press Limited.