DNA polymerase zeta is required for proliferation of normal mammalian cells.
AuthorsLange SS, Wittschieben JP, Wood RD,
JournalNucleic Acids Res
PubMed ID22319213
'Unique among translesion synthesis (TLS) DNA polymerases, pol ? is essential during embryogenesis. To determine whether pol ? is necessary for proliferation of normal cells, primary mouse fibroblasts were established in which Rev3L could be conditionally inactivated by Cre recombinase. Cells were grown in 2% O(2) to prevent oxidative stress-induced ... More
Pharmacologic profiling of phosphoinositide 3-kinase inhibitors as mitigators of ionizing radiation-induced cell death.
AuthorsLazo JS, Sharlow ER, Epperly MW, Lira A, Leimgruber S, Skoda EM, Wipf P, Greenberger JS,
Journal
PubMed ID24068833
Ionizing radiation (IR) induces genotoxic stress that triggers adaptive cellular responses, such as activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling cascade. Pluripotent cells are the most important population affected by IR because they are required for cellular replenishment. Despite the clear danger to large population centers, we still lack safe ... More
The efficacy of CHK1 inhibitors is not altered by hypoxia, but is enhanced after reoxygenation.
Inhibitors of CHK1 are in clinical trials for cancer treatment in combination with DNA-damaging agents. Importantly, it was previously suggested that hypoxic cancer cells may be particularly sensitive to CHK1 inhibition. However, this suggestion was based on studies in severe, toxic levels of hypoxia (anoxia). The influence of less severe ... More
Systems biology approach identifies the kinase Csnk1a1 as a regulator of the DNA damage response in embryonic stem cells.
AuthorsCarreras Puigvert J, von Stechow L, Siddappa R, Pines A, Bahjat M, Haazen LC, Olsen JV, Vrieling H, Meerman JH, Mullenders LH, van de Water B, Danen EH,
JournalSci Signal
PubMed ID23354688
In pluripotent stem cells, DNA damage triggers loss of pluripotency and apoptosis as a safeguard to exclude damaged DNA from the lineage. An intricate DNA damage response (DDR) signaling network ensures that the response is proportional to the severity of the damage. We combined an RNA interference screen targeting all ... More
AuthorsKridel R, Meissner B, Rogic S, Boyle M, Telenius A, Woolcock B, Gunawardana J, Jenkins C, Cochrane C, Ben-Neriah S, Tan K, Morin RD, Opat S, Sehn LH, Connors JM, Marra MA, Weng AP, Steidl C, Gascoyne RD,
JournalBlood
PubMed ID22210878
Mantle cell lymphoma (MCL), an aggressive subtype of non-Hodgkin lymphoma, is characterized by the hallmark translocation t(11;14)(q13;q32) and the resulting overexpression of cyclin D1 (CCND1). Our current knowledge of this disease encompasses frequent secondary cytogenetic aberrations and the recurrent mutation of a handful of genes, such as TP53, ATM, and ... More