Exposure to environmental agents and endogenous metabolites and cancer chemotherapy can give rise to DNA interstrand cross-link lesions.  In this presentation, I will discuss our application of shuttle vector methods to examine the efficiency and fidelity with which DNA interstrand cross-link-containing plasmids are replicated in cultured human cells that are proficient in translesion synthesis or the isogenic cells deficient in individual translesion synthesis DNA polymerases.  We will demonstrate that the shuttle vector-based studies provided important molecular level understanding about how DNA interstrand cross-link lesions impede DNA replication and induce mutagenesis in human cells as well as about how individual translesion synthesis DNA polymerases function in replication across these lesions.  Additionally, we will describe the use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the quantitative measurements of DNA interstrand cross-link lesions in mammalian cells and for assessing the repair of these lesions.<br/>

Replication and repair of DNA interstrand cross-link lesions in human cells

254th National Meeting (2017)

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