Cisplatin-induced alterations in the expression of the mRNAs for UV-damage recognition protein.
Enhanced DNA repair is believed to be an important mechanism of the cisplatin-resistant phenotype. UV-damage recognition protein (UV-DRP) recognizes and binds to DNA lesions and may play a role in DNA nucleotide excision repair and/or replicative bypass (which is associated with post-replication repair). Potential alternations in the expression of mRNAs for UV-DRP were analyzed in this study. Two pairs of parental and cisplatin-resistant human ovarian carcinoma cell lines were utilized. Gene expression level was assessed by northern blot hybridization. No alterations in mRNA levels for the large subunit of UV-DRP were found following cisplatin treatment, whereas mRNA levels for the small subunit of UV-DRP were induced up to 4.5-fold. The time-course and concentration-response of this induction corresponded to the previously reported increase in the UV-DRP binding activity, as measured by gel shift assay. UV-DRP binding activity in cell extracts corresponds to expression of small subunit mRNA but not to expression of large subunit mRNA. These data suggest that the small subunit may be limiting for UV-DRP activity.
Vaisman
A
A
Department of Biochemistry & Biophysics, School of Medicine, University of North Carolina, Chapel Hill 27599-7260, USA.
Keeney
S
S
Nichols
A F
AF
Linn
S
S
Chaney
S G
SG
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D002277:Carcinoma / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; C091435:DDB1 protein, human; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D002945:Cisplatin