Publications by authors named "M Nieborowska-Skorska"
Myeloid malignancies carrying somatic DNMT3A mutations (DNMT3Amut) are usually resistant to standard therapy. DNMT3Amut leukemia cells accumulate toxic DNA double strand breaks (DSBs) and collapsed replication forks, rendering them dependent on DNA damage response (DDR). DNA polymerase theta (Polθ), a key element in Polθ-mediated DNA end-joining (TMEJ), is essential for survival and proliferation of DNMT3Amut leukemia cells.
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- DNA polymerase theta (Polθ) is a protein involved in repairing DNA double-strand breaks and helps cells resist harmful agents.
- The regulation of Polθ's activity in this repair process, known as TMEJ (Theta-Mediated End Joining), involves a two-step mechanism where PARP1 first attaches a modification (PARylation) to Polθ, bringing it to damage sites but rendering it inactive.
- The enzyme PARG then removes this modification, restoring Polθ's ability to bind DNA and perform the repair, making PARG crucial for the activation of TMEJ in response to DNA damage.
Unlabelled: DNA polymerase theta (Polθ, encoded by POLQ gene) plays an essential role in Polθ-mediated end-joining (TMEJ) of DNA double-strand breaks (DSB). Inhibition of Polθ is synthetic lethal in homologous recombination (HR)-deficient tumor cells. However, DSBs can be also repaired by PARP1 and RAD52-mediated mechanisms.
View Article and Find Full Text PDFDeletion of ABL1 was detected in a cohort of hematologic malignancies carrying AML1-ETO and NUP98 fusion proteins. Abl1-/- murine hematopoietic cells transduced with AML1-ETO and NUP98-PMX1 gained proliferation advantage when compared to Abl1 + /+ counterparts. Conversely, overexpression and pharmacological stimulation of ABL1 kinase resulted in reduced proliferation.
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