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Defective DNA repair by homologous recombination (HR) is thought to be a major contributor to tumorigenesis in individuals carrying Brca1 mutations. Here, we show that DNA breaks in Brca1-deficient cells are aberrantly joined into complex chromosome rearrangements by a process dependent on the nonhomologous end-joining (NHEJ) factors 53BP1 and DNA ligase 4.(More)
Akt kinase is activated by transforming growth factor-beta1 (TGF-beta) in diabetic kidneys, and has important roles in fibrosis, hypertrophy and cell survival in glomerular mesangial cells. However, the mechanisms of Akt activation by TGF-beta are not fully understood. Here we show that TGF-beta activates Akt in glomerular mesangial cells by inducing the(More)
Chromosomal double strand breaks (DSBs) can be repaired by a number of mechanisms that result in diverse genetic outcomes. To examine distinct outcomes of chromosomal DSB repair, a panel of human cell lines has been developed that contain GFP-based reporters with recognition sites for the rare-cutting endonuclease I-SceI. One set of reporters is used to(More)
To characterize the repair pathways of chromosome double-strand breaks (DSBs), one approach involves monitoring the repair of site-specific DSBs generated by rare-cutting endonucleases, such as I-SceI. Using this method, we first describe the roles of Ercc1, Msh2, Nbs1, Xrcc4, and Brca1 in a set of distinct repair events. Subsequently, we considered that(More)
BACKGROUND RNF168 promotes chromosomal break localization of 53BP1 and BRCA1; 53BP1 loss rescues homologous recombination (HR) in BRCA1-deficient cells. RESULTS RNF168 depletion suppresses HR defects caused by BRCA1 silencing; RNF168 influences HR similarly to 53BP1. CONCLUSION RNF168 is important for HR defects caused by BRCA1 loss. SIGNIFICANCE(More)
Figure S1 Dose response and time course of the effects of TGF-on RNA levels of various genes. Dose response. MMC were treated with 0, 2, 5 or 10 ng/ml of TGF- for 24 hours. Expression levels of miR-192 (a), RP23 (b), miR-216a (c), miR-217 (d), Zeb1 (e), Zeb2 (f), Col1a2 (g) and Pten (h) were examined by RT-qPCR (mean and s.e.m., n=3). Time course. MMC(More)
During repair of multiple chromosomal double strand breaks (DSBs), matching the correct DSB ends is essential to limit rearrangements. To investigate the maintenance of correct end use, we examined repair of two tandem noncohesive DSBs generated by endonuclease I-SceI and the 3' nonprocessive exonuclease Trex2, which can be expressed as an I-SceI-Trex2(More)
In pain management as well as other clinical applications of neuromodulation, it is important to consider the timing parameters influencing activity-dependent plasticity, including pulsed versus sustained currents, as well as the spatial action of electrical currents as they polarize the complex convolutions of the cortical mantle. These factors are of(More)
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