XPA versus ERCC1 as chemosensitising agents to cisplatin and mitomycin C in prostate cancer cells: Role of ERCC1 in homologous recombination repair

The XPA-binding domain of ERCC1 Is Required for Nucleotide Excision Repair but Not Other DNA Repair Pathways

“…A common perception is that this resistance to cisplatin is due to enhanced levels of NER (63). By contrast, other studies have indicated that the treatment of cells with small interfering RNA against ERCC1, but not against XPA, renders cells sensitive to cross-linking agents (64). Our studies show directly that a defect in the interaction between ERCC1 and XPA that disrupts NER has no major effect on the cellular sensitivity to the chemotherapeutic agents cisplatin and mytomycin C. It therefore appears that NER mediated by ERCC1 is not a key determinant of cellular sensitivity to cisplatin.…”

Repair Capacity for Platinum-DNA Adducts Determines the Severity of Cisplatin-Induced Peripheral Neuropathy

“…The ICA method used in this study is not applicable to discriminate between the two NER subpathways at the level of individual cells. Comparison of the adduct kinetics revealed two unexpected results: (1) peak levels of Pt-(GG) adducts in DRG cells were nearly twofold higher in both knock-out strains compared with WT mice, indicating that NER functions already interfere with very early steps of cross-link formation, and (2) XPA-deficient cells, which have been shown to be completely deprived of repairing UV-induced dimers in DNA, were still capable to reduce the level of Pt-(GG) lesions by ϳ30% within 4 d. Although a previous study with siRNA-mediated downregulation of XPA in cisplatin-exposed cell lines suggested that recombination repair functions might be able to partly substitute for impaired NER (Cummings et al, 2006), such an activity has not yet been described in G 0 cells. Therefore, the precise mechanism of the XPA-independent global genomic repair of cisplatin-DNA cross-links has to be further investigated.…”

Applications of Fluorescence for Detecting Rare Sequence Rearrangements In Vivo

“…[39][40][41][42] Therefore, knowledge about HR capacity is relevant both to one's risk of developing cancer 13,14,19 and to the response of a tumor to chemotherapy. [39][40][41][42][43] Although HR is an important pathway for overcoming the potential lethality and mutagenicity of replicative stress, studying HR has been difficult since many key HR proteins are either essential for viability [44][45][46][47][48][49] or possibly sufficiently redundant that their absence does not fully reveal the role of this pathway in vivo. An alternative approach for studying HR is to measure DNA sequence rearrangements that result from HR events.…”