ABSTRACT
For understanding the molecular mechanism one can also adopt in silico approach where the interactions such as Protein-protein interactions, Protein-compound interactions, DNA-compound interactions, DNA-protein interactions are commonly used. Here we focused on the fate of these interactions for some of the compounds of Emblica officinalis with normal DNA polymerase β. Efficacy of these compounds involves design/taking from the databases of these molecules that are probable to act on the bimolecular target. DNA polymerase beta protein PDB (1DK3) was used to dock with compounds like Quercetin, Myricetin and 3,7,3,4-Tetra Hydroxy Flavone. All these compounds showed best binding studies with DNA polymerase beta.
ABSTRACT
Objective: To investigate the effects of silencing DNA polymerase β by small interfering RNA (siRNA) on the proliferation of human gastric cancer cell line BGC-823. Methods: Various siRNA expression vectors were constructed and transfected into BGC-823 cells. The expression levels of pol β mRNA and protein were detected by real-time PCR and Western blotting, respectively. The proliferation of BGC-823 cells was detected by flow cytometry in vitro and evaluated by tumor formation test in nude mice. Results: The expression levels of polβ mRNA and protein were obviously reduced in experimental group transfected with pol β-targeted siRNA expression vectors, and the silencing degree of pRNAT-U6. 1-sipolβ2 vector was stronger than that of pRNAT-U6. 1-sipolβ1 vector (83% vs 56%). Compared with irrelevant siRNA control group, empty vector control group, and un-transfected group, the proportion of cells in S phase and cell proliferation speed significantly decreased in pRNAT-U6. 1-sipolβ1 transfection group (P < 0.05); on the contrary, the proportion of cells in S phase and cell proliferation speed significantly increased in pRNAT-U6. 1-sipolβ2 transfection group (P < 0.05). Conclusion: Over-expression or nearly complete inhibition of expression of polβ has no benefit to maintain the cells normal physiological functions. The tumor growth could be inhibited by silencing the expression of pol β by siRNA to appropriate low level.
ABSTRACT
Objective To study the change of DNA polymerase beta and XRCC1's expression during malignant celI differentiation.Methods The Eca-109 cells were divided inm 2 groups:differentiation group which cultured with 8-Br-cAMP and control group.The 2 groups cells were cultured 48h simultaneously.The immunocytochemistry was performed to detect the expression of DNA polymerase beta and XRCC1.Results Compared with control group,the expression of DNA polymerase beta and XRCC1 was decreased simultaneously(P＜0.05).Conclusion The differentiation agent can down-regulate the expression of DNA polymerase beta and XRCC1,suggesting that overexpressed DNA polymerase beta and XRCC1 maybe result in mutator phenotype.
ABSTRACT
The p53 tumor suppressor has long been envisaged to preserve genetic stability by the induction of cell cycle checkpoints and apoptosis. More recently, p53 has been implicated to play roles in DNA repair responses to genotoxic stresses. UV-damage and the damage caused by certain chemotherapeutics including cisplatin and nitrogen mustards are known to be repaired by the nucleotide excision repair (NER) pathway which is reportedly regulated by p53 and its downstream genes. There are evidences to suggest that the base excision repair (BER) induced by the base-damaging agent methyl methanesulfonate (MMS) is partially deficient in cells lacking functional p53. This result suggests that the activity of BER might be also dependent on the p53 status. In this review, we discuss the possibilities that p53 regulates BER as well as NER; these are one of the most significant potentials of p53 tumor suppressor for repairing the vast majority of DNA damages that is incurred from various environmental stresses.