title: A computational approach to determine susceptibility to cancer by evaluating the deleterious effect of nsSNP in XRCC1 gene on binding interaction of XRCC1 protein with ligase III.
abstract: Several reports suggest that non-synonymous single nucleotide polymorphisms affect the function of XRCC1 which impairs DNA repair capacity and thus increases risk to diseases like cancer. In our study, we predicted the most damaging nsSNPs using a computational approach and analysed its functional impact on the XRCC1 and LIG3 interaction. SNP rs2307166 was predicted to be deleterious using eight software programs: SIFT, PolyPhen, PANTHER, PhD-SNP, nsSNPAnalyzer, SNPS&GO, SNAP and I-Mutant. Protein structural analysis was performed using Swiss PDB viewer, and PyMOL. Xenoview was used for molecular dynamic simulation and energy minimisation. Finally, PatchDock and FireDock were used to analyse the interactions of XRCC1 and LIG3. By comparing the results we found that the mutant protein has less binding energy and the interacting amino acids than native protein. In silico analysis predicted rs2307166 to be more damaging than three other extensively studied SNPs. Identification of this SNP will help in determining the susceptibility of the individual to cancer, their prognosis and further treatment.
authors.affiliation: Ashok and Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences (ARIBAS), New Vallabh Vidyanagar, Sardar Patel University, Anand, Gujarat 388121, India.
authors.forename: Preety Kadian
authors.initials: PK
authors.lastname: Singh
authors.affiliation: Ashok and Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences (ARIBAS), New Vallabh Vidyanagar, Sardar Patel University, Anand, Gujarat 388121, India. Electronic address: kinnarimistry@aribas.edu.in.
authors.forename: Kinnari N
authors.initials: KN
authors.lastname: Mistry
mesh_terms: D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D030562:Databases, Protein; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D020539:Sequence Analysis, Protein / Q000379:methods; D012984:Software; D000076105:X-ray Repair Cross Complementing Protein 1; D029867:Xenopus Proteins
chemical_list: D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D029867:Xenopus Proteins; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus; C000618817:LIG3 protein, human
keywords: DNA repair; Deleterious; In silico; Mutant; Phenotype