The inhibitory effect of HMGB-1 protein on the repair of cisplatin-damaged DNA is accomplished through the acidic domain.
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.
Mitkova
Elena
E
Institute of Molecular Biology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Ugrinova
Iva
I
Pashev
Iliya G
IG
Pasheva
Evdokia A
EA
D000818:Animals; D045744:Cell Line, Tumor; D002474:Cell-Free System; D002945:Cisplatin / Q000378:metabolism / Q000633:toxicity; D018736:DNA Adducts / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004563:Electrochemistry; D024243:HMGB1 Protein / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D017434:Protein Structure, Tertiary
D018736:DNA Adducts; D024243:HMGB1 Protein; C057270:cisplatin-DNA adduct; D002945:Cisplatin