EndoG and ATM cell cycle checkpoint in Leukemogenesis
In a recent publication, Gole B. and Baumann C. demonstrate the role of the apoptotic nuclease EndoG in Mixed-Lineage Leukemia breakpoint cluster region (MLLbcr) destabilisation leading to MLL gene rearrangements and leukemogenesis. (1)
In this study, various engineered stable knockdown cell lines were used as in vitro cellular models. Two of them are developed by tebu-bio: SilenciX® HeLa/shATM and HeLa/shATR. They have been selected as stable ATM and ATR KD cellular models to investigate the role of ATM (Ataxia Telangiectasia, Mutated) and ATR (ATM and Rad3-related) cell cycle checkpoint pathways in these MLL rearrangements.
The authors also describe a possible cytotoxic-induced model involving EndoG and ATM / RFN20 / H2B cascade in MLLbcr breakage.
About SilenciX stable KD HeLa cells
SilenciX are gene-specific knock-down (KD) engineered HeLa cell lines. The silencing technology used is not integrative, reducing thus potential off-target effects. These KD cellular models are ideal for a broad range of signal transduction and drug discovery studies (Loss-of-function model, Synthetic lethality…). To date, 100+ HeLa SilenciX cell lines have been designed (customization on other cell types being possible). Recently, BRCA1-KD, BRCA2-KD and p53-KD SilenciX HeLa cells were used to show that PARP inhibitors are less synthetically lethal in hypoxic conditions. (2)
SilenciX® is a registered trademark of tebu-bio; technology licensed from the Atomic Energy and Alternative Energies Commission (CEA). (3)
(1) Gole B., Baumann C. et al. “Endonuclease G initiates DNA rearrangements at the MLL breakpoint cluster upon replication stress” (2014) Oncogene, pp-1-11. DOI:10.1038/onc.2014.268.
(2) Mennesson E. et al. ‘SilenciX®, novel stable knock-down cellular models to screen new molecular targets through the synthetic lethality approach” (2014) (“Experimental and Molecular Therapeutics” poster session – AACR 2014, San Diego – Abstract n° 3733.
Typical silencing results with HeLa and custom cell lines
I hope these data will bring you new opportunities for your research programs. Share this post or leave any comments concerning the tools you are using to perform efficient and robust gene KD below!