Enhanced nucleotide excision repair capacity in lung cancer cells by preconditioning with DNA-damaging agents

Oncotarget
Ji Ye ChoiTae-Hong Kang

Abstract

The capacity of tumor cells for nucleotide excision repair (NER) is a major determinant of the efficacy of and resistance to DNA-damaging chemotherapeutics, such as cisplatin. Here, we demonstrate that using lesion-specific monoclonal antibodies, NER capacity is enhanced in human lung cancer cells after preconditioning with DNA-damaging agents. Preconditioning of cells with a nonlethal dose of UV radiation facilitated the kinetics of subsequent cisplatin repair and vice versa. Dual-incision assay confirmed that the enhanced NER capacity was sustained for 2 days. Checkpoint activation by ATR kinase and expression of NER factors were not altered significantly by the preconditioning, whereas association of XPA, the rate-limiting factor in NER, with chromatin was accelerated. In preconditioned cells, SIRT1 expression was increased, and this resulted in a decrease in acetylated XPA. Inhibition of SIRT1 abrogated the preconditioning-induced predominant XPA binding to DNA lesions. Taking these data together, we conclude that upregulated NER capacity in preconditioned lung cancer cells is caused partly by an increased level of SIRT1, which modulates XPA sensitivity to DNA damage. This study provides some insights into the molecular mec...Continue Reading

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Citations

Dec 11, 2019·International Journal of Molecular Sciences·Tae-Hee Lee, Tae-Hong Kang
Jan 6, 2018·Biomedicines·Ilya O VelegzhaninovOlesya M Vakhrusheva
Apr 3, 2020·International Journal of Molecular Sciences·Lucia Borszéková PulzováMiroslav Chovanec
Mar 7, 2020·The Journal of Clinical Investigation·Manchao ZhangFen Xia
Oct 3, 2019·Anais Da Academia Brasileira De Ciências·Marcia R SchneiderAndreia R M Valim
Jun 3, 2021·Biomolecules·Tae-Hong Kang

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Methods Mentioned

BETA
Assay
acetylation
immunoprecipitation

Software Mentioned

NIS
GraphPad Prism
Elements

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