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DNA Damage Response Research, Inherent and Future Nano-Based Interfaces for Personalized Medicine
Published in Yubing Xie, The Nanobiotechnology Handbook, 2012
Madhu Dyavaiah, Lauren Endres, Yiching Hsieh, William Towns, Thomas J. Begley
The 9-1-1 complex structurally resembles a doughnut-shaped homotrimeric complex like the proliferating cell nuclear antigen (PCNA). The 9-1-1 complex serves as a sliding clamp that encircles DNA and loads other enzymes on stalled replication forks to accommodate specific checkpoint, repair, and tolerance responses to DNA damage. The 9-1-1 complex contains an elliptical hole that is of sufficient size to accommodate the presence of double-stranded DNA that is 2.4 nm in diameter. The elliptical hole is formed around interactions between Rad9-Hus1, Rad9-Rad1, and Rad1-Hus1 (Dore et al. 2009). Like the 9-1-1 complex, PCNA is also a processivity factor that resembles a doughnut. PCNA encircles DNA at sites of DNA replication and DNA repair and essentially threads DNA through a central hole that is ∼3.4 nm in diameter (Ivanov et al. 2006). Both PCNA and the 9-1-1 complex are thus nanopore-based structures vital to DNA integrity. These nanopores serve as docking and coordination stations to attract and stimulate potential response proteins. Signaling from the 9-1-1 nanopore requires Rad17, which not only forms a complex with replication factor C to assist the 9-1-1 complex in loading onto and around the DNA but is also critical for the ATM and Rad3-related (ATR)-dependent activation (Lee and Dunphy 2010). The MRN and 9-1-1 complexes initially detect the DNA lesions or stalled replication fork and then trigger or recruit the phosphatidylinositol 3-kinase-like protein kinase (PIKK) family members—ATM (ataxia telangiectasia mutated) and ATR onto chromatin.
Iron
Published in Yoshinobu Onuma, Patrick W.J.C. Serruys, Bioresorbable Scaffolds, 2017
Runlin Gao, Deyuan Zhang, Hong Qiu, Chao Wu, Ying Xia, Gui Zhang
PCNA plays an important role in promoting cell division and proliferation, and its expression level is directly proportional to cell proliferation activity. At each time point, PCNA expression positivity did not differ significantly between the iron scaffold and control groups, indicating similar cell proliferative activity between the two groups.
Possible ameliorating effect of isoquercetin on diethylnitrosamine-induced hepatocellular carcinoma in albino mice
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Kholoud A. Omran, Yomna I. Mahmoud, Asmaa A. Mahmoud, Nagui H. Fares
VEGF is an endothelial growth factor that regulates angiogenesis and is critical for HCC growth and development [43]. In DEN-induced carcinogenesis is overexpressed [44,45]. Angiogenesis can be triggered by activation of oncogenes like ras or inactivation of tumor suppressor genes like p53 [46]. An increased level of PCNA expression has been described to signify an aggressive tumor [47]. Many studies reported overexpression of PCNA in DEN-induced carcinogenesis [48].