Identification of inducible damage-recognition proteins that are overexpressed in HeLa cells resistant to cis-diamminedichloroplatinum (II)

Abstract

Two cis-diamminedichloroplatinum (II) (cisplatin)-inducible proteins [b 130 (approximately 130 kDa) and b95 (approximately 95 kDa]) in HeLa cells that recognize both the cisplatin-modified and u.v.-modified DNA were identified in this study. These damage-recognition proteins were overexpressed in cisplatin-resistant HeLa cells. The results suggest that the damage-recognition proteins are regulated in the cells in response to DNA damage, and they may be important for DNA repair and probably the emergence of cisplatin resistance.

Cisplatin-DNA damage recognition proteins in human tumour extracts

“…There have been reported of increased levels of damage recognition proteins binding to UV-damaged DNA in CDDPresistant cell lines (Chu & Chang, 1990;Chao et al, 1991c) and of induction of these proteins by exposure to CDDP (Chao et al, 1991c). However Andrews and Jones (1991) showed no correlation between the level of CDDP-damage recognition proteins in ovarian carcinoma cell lines, including A2780 and A2780CP, and their sensitivity to CDDP.…”

“…CDDP-DNA adducts can also be repaired in vitro by cell free extracts from mammalian cells (Hansons & Wood, 1989). Although the nucleotide excision repair system in eukaryotic cells is incompletely characterised, mammalian proteins have been identified which recognise and bind to DNA damaged by various agents including CDDP (Chu & Chang, 1988;Donahue et al, 1990;Toney et al, 1989;Chao et al, 1991c). It has been postulated that these damage recognition proteins may be involved in the initial steps of excision repair, or alternatively may block access of repair enzymes to the sites of DNA damage.…”

“…There is evidence that increased expression of damage recognition proteins may correlate with CDDP resistance (CHu & Chang, 1990;Chao et al, 1991c;McLaughlin et al, 1992). This paper describes the identification of CDDPdamage recognition proteins in cell extracts from human tumour cell lines and tumour biopsies using gel-mobility shift and southwestern blot assays.…”

Correction of the DNA repair defect in xeroderma pigmentosum group E by injection of a DNA damage-binding protein.

“…However, there was only indirect evidence for a role of the DDB protein in DNA repair (8)(9)(10)(11). Moreover, a high-mobility-group 1 protein recognizes damaged DNA and binds cisplatin adducts (26,27).…”

“…This stable heterodimer can, in turn, form a higher order complex (5,7). The role of the DDB protein in nucleotide-excision repair is not known; indeed, there is as yet only indirect evidence that it is involved in DNA repair at all (8)(9)(10)(11).…”