C http www apexbt com media diy images wb

C136 is present in the joining region of two domains of NEIL1 and plays a critical role in the stability and dynamics of enzyme (Roy et al., 2007, Prakash et al., 2014). E181 resides in the conserved H2TH motif that binds to DNA and is very essential for enzyme activity. C136 is present in the near proximity of R277, P2, and K54 that form the active site for the catalysis. The PDB structure (1TDH) shows that residues G83, S82, G245 and D252 are in proximity and may form an environment favorable for enzyme activity. So, their interaction may have role in enzyme function (Fig. 7, Fig. 8). All the BMS-650032 are highly conserved and their alteration would lead to decrease in the activity and DNA repair ability and results in the development of disease like cancer.
MicroRNAs (miRNAs) are small non-coding RNAs that are involved in RNA silencing. They function as guide molecules and target most protein-coding transcripts. MiRNAs are involved in almost all developmental and pathological processes in humans. The biosynthesis of miRNAs is under firm control, and their dysregulation is associated with many human diseases, especially cancer (Minju & Kim, 2014). Polymorphisms in 3′ UTR and 5′ UTR can modify miRNA binding sites and indirectly influence the expression of proteins in the cell. Fifteen SNPs are reported to be present in 3’UTR region and only one SNP (rs4555122) is depicted to be associated with disease in miRNA binding region by miRdSNP database. The list of poorly conserved target miRNAs of NEIL1 gene predicted by TargetScanHuman online tool (http://www.targetscan.org/) is given in Table 3. No conserved miRNA targets were found.
Conclusion
Conflict of interest
Acknowledgement
Introduction Modification of bases in DNA is a common occurrence in cells and one with potentially serious mutagenic consequences. One of the most common modifications is oxidation of guanine. 7,8-Dihydro-8-oxoguanine (8-oxo-G) base-pairs equally well with cytosine and adenine, leading to GC→TA transversions. Virtually all organisms have a glycosylase that recognizes and removes 8-oxo-G from DNA, leading to its replacement by unmodified G through the subsequent reactions of the base-excision repair pathway. In archaea, fungi, and animals, the effective glycosylase is oxoguanine glycosylase (OGG); in bacteria, it is formamidopyrimidine glycosylase (FPG). Plants, uniquely, have genes for both enzymes. Furthermore, plant cells have variants of the mRNA for FPG produced by alternative splicing [1], [2]. The reason for the retention in plants of the genes for both OGG and FPG and the diversity of FPG variants is not known. It is reasonable to speculate that the presence of photosynthetic metabolism, with the resulting high concentration of diatomic oxygen and oxygen radicals, creates a particular need for protection of the genome against oxidative damage. However, knock-out mutants that lack genes for either OGG or FPG, or both, show no obvious phenotype over several generations [3], so the adaptive value of the genes must be subtle or important under unusual circumstances that have not yet been identified. It is also possible that the presence of two analogous genes has allowed one or both to alter the specificity of their protein products, allowing them to recognize additional base modifications. It is known that the glycosylases can have multiple specificities. Bacterial FPG was first shown to act on ring-opened purines [4]. To test the specificities of the plant enzymes, we have inserted cDNAs for OGG and FPG from Arabidopsis thaliana into Escherichia coli strains, devised by Cupples and Miller [5] to test for single-base substitution mutations, in which the endogenous FPG gene has been inactivated [6]. There are six Cupples and Miller [5] strains, each with a base-pair substitution in its LacZ gene that inactivates the product β-galactosidase. Reversion mutations at that base-pair can be easily detected by the recovery of β-galactosidase activity (Table 1). If reversions are initiated by damage to the DNA that can be repaired by plant OGG or FPG, we expect that strains containing the Arabidopsisogg or fpg genes will show less frequent reversion. We report that for both OGG and the primary form of FPG a major activity is the prevention of GC→TA transversions, indicating that both genes retain their original specificities. There is also evidence for other anti- and pro-mutagenic activities of the two enzymes.