@article{ma_halweg_menendez_resnick_2012, title={Differential effects of poly(ADP-ribose) polymerase inhibition on DNA break repair in human cells are revealed with Epstein-Barr virus}, volume={109}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.1118078109}, DOI={10.1073/pnas.1118078109}, abstractNote={Poly(ADP-ribose) polymerase (PARP) inhibitors can generate synthetic lethality in cancer cells defective in homologous recombination. However, the mechanism(s) by which they affect DNA repair has not been established. Here we directly determined the effects of PARP inhibition and PARP1 depletion on the repair of ionizing radiation-induced single- and double-strand breaks (SSBs and DSBs) in human lymphoid cell lines. To do this, we developed an in vivo repair assay based on large endogenous Epstein–Barr virus (EBV) circular episomes. The EBV break assay provides the opportunity to assess quantitatively and simultaneously the induction and repair of SSBs and DSBs in human cells. Repair was efficient in G1 and G2 cells and was not dependent on functional p53. shRNA-mediated knockdown of PARP1 demonstrated that the PARP1 protein was not essential for SSB repair. Among 10 widely used PARP inhibitors, none affected DSB repair, although an inhibitor of DNA-dependent protein kinase was highly effective at reducing DSB repair. Only Olaparib and Iniparib, which are in clinical cancer therapy trials, as well as 4-AN inhibited SSB repair. However, a decrease in PARP1 expression reversed the ability of Iniparib to reduce SSB repair. Because Iniparib disrupts PARP1–DNA binding, the mechanism of inhibition does not appear to involve trapping PARP at SSBs.}, number={17}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Ma, W. and Halweg, C. J. and Menendez, D. and Resnick, M. A.}, year={2012}, month={Apr}, pages={6590–6595} }
 @article{haugen_di prospero_parker_fannin_chou_meyer_halweg_collins_durr_fischbeck_et al._2010, title={Altered Gene Expression and DNA Damage in Peripheral Blood Cells from Friedreich's Ataxia Patients: Cellular Model of Pathology}, volume={6}, ISSN={1553-7404}, url={http://dx.doi.org/10.1371/journal.pgen.1000812}, DOI={10.1371/journal.pgen.1000812}, abstractNote={The neurodegenerative disease Friedreich's ataxia (FRDA) is the most common autosomal-recessively inherited ataxia and is caused by a GAA triplet repeat expansion in the first intron of the frataxin gene. In this disease, transcription of frataxin, a mitochondrial protein involved in iron homeostasis, is impaired, resulting in a significant reduction in mRNA and protein levels. Global gene expression analysis was performed in peripheral blood samples from FRDA patients as compared to controls, which suggested altered expression patterns pertaining to genotoxic stress. We then confirmed the presence of genotoxic DNA damage by using a gene-specific quantitative PCR assay and discovered an increase in both mitochondrial and nuclear DNA damage in the blood of these patients (p<0.0001, respectively). Additionally, frataxin mRNA levels correlated with age of onset of disease and displayed unique sets of gene alterations involved in immune response, oxidative phosphorylation, and protein synthesis. Many of the key pathways observed by transcription profiling were downregulated, and we believe these data suggest that patients with prolonged frataxin deficiency undergo a systemic survival response to chronic genotoxic stress and consequent DNA damage detectable in blood. In conclusion, our results yield insight into the nature and progression of FRDA, as well as possible therapeutic approaches. Furthermore, the identification of potential biomarkers, including the DNA damage found in peripheral blood, may have predictive value in future clinical trials.}, number={1}, journal={PLoS Genetics}, publisher={Public Library of Science (PLoS)}, author={Haugen, Astrid C. and Di Prospero, Nicholas A. and Parker, Joel S. and Fannin, Rick D. and Chou, Jeff and Meyer, Joel N. and Halweg, Christopher and Collins, Jennifer B. and Durr, Alexandra and Fischbeck, Kenneth and et al.}, editor={Pearson, Christopher E.Editor}, year={2010}, month={Jan}, pages={e1000812} }
 @article{halweg_thompson_spiker_2005, title={The rb7 matrix attachment region increases the likelihood and magnitude of transgene expression in tobacco cells: A flow cytometric study}, volume={17}, ISSN={["1532-298X"]}, DOI={10.1105/tpc.104.028100}, abstractNote={Many studies in both plant and animal systems have shown that matrix attachment regions (MARs) can increase expression of transgenes in whole organisms or cells in culture. Because histochemical assays often indicate variegated transgene expression, a question arises: Do MARs increase transgene expression by increasing the percentage of cells expressing the transgene (likelihood), by increasing the level of expression in expressing cells (magnitude), or both? To address this question, we used flow cytometry to measure green fluorescent protein (GFP) expression in individual tobacco (Nicotiana tabacum) cells from lines transformed by Agrobacterium tumefaciens. We conclude that MAR-mediated overall increases in transgene expression involve both likelihood and magnitude. On average, cell lines transformed with the Rb7 MAR-containing vector expressed GFP at levels 2.0- to 3.7-fold higher than controls. MAR lines had fewer nonexpressing cells than control lines (10% versus 45%), and the magnitude of GFP expression in expressing cells was greater in MAR lines by 1.9- to 2.9-fold. We also show that flow cytometry measurements on cells from isogenic lines are consistent with those from populations of independently transformed cell lines. By obviating the need to establish isogenic lines, this use of flow cytometry could greatly simplify the evaluation of MARs or other sequence elements that affect transgene expression.}, number={2}, journal={PLANT CELL}, author={Halweg, C and Thompson, WF and Spiker, S}, year={2005}, month={Feb}, pages={418–429} }