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The goal of our research is to clarify how alterations in genomic and epigenomic stability of CpG sequences lead to altered development and cancer formation. Mutations are often the consequence of defective DNA repair; we are particularly interested in the mammalian DNA repair enzymes that protect the integrity of CpG sequences in DNA: MBD4 and TDG. This is important because mutations at CpG sites represent about one third of all point mutations in cancer. In addition, CpG sites are also important for regulation of gene activity by an epigenetic process called DNA methylation. We discovered a role of TDG in active DNA demethylation (Cortellino et al. Cell, 2011), which is highly relevant in the context of the recently identified oxidized cytosine variants that have expanded the information content of the genome: TDG is the only enzyme that efficiently removes 5-formylcytosine and 5-carboxylcytosine produced by the TET dioxygenases.
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EUROPEAN JOURNAL OF HUMAN GENETICS (2024): 67-67
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