Biochem P53

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DNA Mediated Charge Transport in p53

CHM 4390-U02
Rohit Vinod
April 22, 2015
INTRODUCTION
Human transcription factor p53 is considered to be an important and useful protein that plays a key role in cancer and tumor suppression. Many of the pathways in which p53 is utilized usually are apoptosis, cell deterioration also known as senescence, cell cycle arrest or DNA repair (Riley et. al, 2008). P53 also plays a role in glucose metabolism as a regulator of glycolytic and oxidative phosphorylation through positive and negative regulation of certain genes and the proteins that they encode for (Madan et. al, 2011). Usually if there are mutations in the genes that eventually translate into p53 then there are significant chance that tumors start to develop as seen in more than half of human cancers. In addition to such necessary roles, p53 also can sense oxidative stress and binds to redox-active DNA which often receives oxidative damage due to election migration through the DNA base stack. Many other sources of DNA oxidation can arise as a result of ionizing radiation, exogenous chemicals and even metabolic side products (Generaux et. al, 2010). DNA can be utilized in charge transport over distances of 100 base pairs or 34 nm in length (Augustyn et. al, 2013). The significance of the DNA oxidation and p53’s ability to sense oxidative stress is essential in understanding how DNA can be utilized in charge transport. In particular, redox activation in p53 occurs using DNA CT and the thiol switches used (Sontz, 2007). P53 was examined due to the protein having 10 cysteine residues where cysteine is often used in vivo by DNA-bound proteins for its redox capabilities. The experiment conducted by Schaefer and Barton (2014) examines how DNA sequence plays in greater detail in terms of selectivity and sequence context. The experimenters hypothesized that guanine…...

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