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The inhibitory effect of HMGB-1 protein on the repair of cisplatin-damaged DNA is accomplished through the acidic domain
Authors:Mitkova Elena  Ugrinova Iva  Pashev Iliya G  Pasheva Evdokia A
Institution:Institute of Molecular Biology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Abstract:The well established inhibitory effect of HMGB-1 on repair of cisplatin-damaged DNA has been studied with two modified forms of the protein, shown to bind platinated DNA with higher affinity than the original protein: in vivo acetylated HMGB-1 and HMGB-1 lacking its C-terminal domain. The native and the modified proteins were assayed for their effects on adduct removal by using cell-free extract capable of repairing cisplatinated DNA in vitro. The inhibition observed with the native HMGB-1 was reduced in the presence of acetylated HMGB-1 and completely abolished when the assay was carried out with the truncated protein. When the repair assay was performed in the presence of a synthetic polypeptide identical to the C-terminal tail, either alone or together with the truncated protein, the inhibitory effect was partially recovered in a concentration-dependent manner. These findings strongly suggest that the HMGB-1-induced inhibition of cisplatin-DNA adduct repair is accomplished through the acidic domain. The results obtained are discussed in terms of the repair events that may occur in the presence of HMGB-1 protein.
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