A Germline Polymorphism of Thymine DNA Glycosylase Induces Genomic Instability and Cellular Transformation

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DNA repair is vital to the survival and propagation of cells. It helps protect DNA from becoming permanently damaged and prevents cells from becoming cancerous. The base excision repair (BER) pathway is responsible for the removal of up to 20,000 lesions/cell/day. Thymine DNA glycosylase (TDG) is one of the DNA glycosylases that initiates BER. There is a germline variant of TDG that is found in 10% of the global population, where amino acid residue glycine 199 is mutated to serine. Here, we provide evidence that TDG variant G199S binds significantly more tightly to its abasic product and leads to increased DNA strand breaks in cells. We go on to show that G199S induces genomic instability, in the form of chromosomal aberrations, and leads to cellular transformation, both hallmarks of tumorigenesis. Collectively, our work suggests that a germline variant of TDG can drive carcinogenesis.

Vyšlo v časopise: A Germline Polymorphism of Thymine DNA Glycosylase Induces Genomic Instability and Cellular Transformation. PLoS Genet 10(11): e32767. doi:10.1371/journal.pgen.1004753
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004753

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