Regulation of the error-prone DNA polymerase polκ by oncogenic signaling and its contribution to drug resistance
UID: 10528
- Description
- Summary from the GEO: "We report how the A375 melanoma cell line changes following CRISPR-Cas9 inactivation of POLK
RNA-seq of A375 melanoma cells following CRISPR-Cas9 with either POLK sgRNA or non-targeting control sgRNA (N=3 replicate samples each)."
Abstract summary From "Regulation of the error-prone DNA polymerase Polκ by oncogenic signaling and its contribution to drug resistance": "The DNA polymerase Polκ plays a key role in translesion synthesis, an error-prone replication mechanism. Polκ is overexpressed in various tumor types. Here, we found that melanoma and lung and breast cancer cells experiencing stress from oncogene inhibition up-regulated the expression of Polκ and shifted its localization from the cytoplasm to the nucleus. This effect was phenocopied by inhibition of the kinase mTOR, by induction of ER stress, or by glucose deprivation. In unstressed cells, Polκ is continually transported out of the nucleus by exportin-1. Inhibiting exportin-1 or overexpressing Polκ increased the abundance of nuclear-localized Polκ, particularly in response to the BRAFV600E-targeted inhibitor vemurafenib, which decreased the cytotoxicity of the drug in BRAFV600E melanoma cells. These observations were analogous to how Escherichia coli encountering cell stress and nutrient deprivation can up-regulate and activate DinB/pol IV, the bacterial ortholog of Polκ, to induce mutagenesis that enables stress tolerance or escape. However, we found that the increased expression of Polκ was not excessively mutagenic, indicating that noncatalytic or other functions of Polκ could mediate its role in stress responses in mammalian cells. Repressing the expression or nuclear localization of Polκ might prevent drug resistance in some cancer cells."
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Access via GEO
GZip and CSV Sequencing Data
Accession #: GSE145313Access via SRARNA Sequence reads for 6 samples.
Accession #: SRP249534Access via BioProjectAdditional information about overall initiative.
Accession #: PRJNA606746 - Access Restrictions
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Free to All
- Access Instructions
- The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
- Associated Publications
- Data Type
- Equipment Used
- Dataset Format(s)
- CSV, SRA, gzip
- Dataset Size
- 335.4 Kb (gzip of CSV), 32.1 Gb (SRA)
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