Publications by authors named "Amelie van der Veen"
The DNA damage response orchestrates the repair of DNA lesions that occur spontaneously, are caused by genotoxic stress, or appear in the context of programmed DNA breaks in lymphocytes. The Ataxia-Telangiectasia Mutated kinase (ATM), ATM- and Rad3-Related kinase (ATR) and the catalytic subunit of DNA-dependent Protein Kinase (DNA-PKcs) are among the first that are activated upon induction of DNA damage, and are central regulators of a network that controls DNA repair, apoptosis and cell survival. As part of a tumor-suppressive pathway, ATM and ATR activate p53 through phosphorylation, thereby regulating the transcriptional activity of p53.
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- The RAG1 and RAG2 proteins are crucial for V(D)J recombination in lymphocytes, as they introduce DNA breaks needed for proper immune receptor development.
- DNA damage, such as from genotoxic stress, triggers the ATM kinase to swiftly downregulate RAG1/2 expression, which helps protect against improper DNA recombination.
- This process involves FOXO1, which under normal conditions helps regulate RAG1/2 expression, but is cleaved and loses its binding capacity to the RAG1/2 enhancer during DNA damage, highlighting a negative feedback mechanism that minimizes risks of aberrant recombinations.