SAMHD1 restrains aberrant nucleotide insertions at repair junctions generated by DNA end joining.

Aberrant end joining of DNA double strand breaks leads to chromosomal rearrangements and to insertion of nuclear or mitochondrial DNA into breakpoints, which is commonly observed in cancer cells and constitutes a major threat to genome integrity. However, the mechanisms that are causative for these insertions are largely unknown. By monitoring end joining of different linear DNA substrates introduced into HEK293 cells, as well as by examining end joining of CRISPR/Cas9 induced DNA breaks in HEK293 and HeLa cells, we provide evidence that the dNTPase activity of SAMHD1 impedes aberrant DNA resynthesis at DNA breaks during DNA end joining.

Re-Sensitizing Tumor Cells to Cancer Drugs with Epigenetic Regulators.

Cancer drug resistance is a major problem for cancer therapy. While many drugs can be effective in first-line treatments, cancer cells can become resistant due to genetic (mutations and chromosomal aberrations) but also epigenetic changes. Hence, many research studies addressed epigenetic drugs in circumventing resistance to conventional therapeutics in different tumor entities and in increasing the efficiency of immune checkpoint therapies.

RNA editing contributes to epitranscriptome diversity in chronic lymphocytic leukemia.

RNA editing-primarily conversion of adenosine to inosine (A > I)-is a widespread posttranscriptional mechanism, mediated by Adenosine Deaminases acting on RNA (ADAR) enzymes to alter the RNA sequence of primary transcripts. Hence, in addition to somatic mutations and alternative RNA splicing, RNA editing can be a further source for recoding events. Although RNA editing has been detected in many solid cancers and normal tissue, RNA editing in chronic lymphocytic leukemia (CLL) has not been addressed so far.