A Gene Expression Signature to Predict Nucleotide Excision Repair Defects and Novel Therapeutic Approaches.

ABSTRACT: Nucleotide excision repair (NER) resolves DNA adducts, such as those caused by ultraviolet light. Deficient NER (dNER) results in a higher mutation rate that can predispose to cancer development and premature ageing phenotypes. Here, we used isogenic dNER model cell lines to establish a gene expression signature that can accurately predict functional NER capacity in both cell lines and patient samples. Critically, none of the identified NER deficient cell lines harbored mutations in any NER genes, suggesting that the prevalence of NER defects may currently be underestimated. Identification of compounds that induce the dNER gene expression signature led to the discovery that NER can be functionally impaired by GSK3 inhibition, leading to synergy when combined with cisplatin treatment. Furth

SUBMITTER: Wei R 

PROVIDER: S-EPMC8125907 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature