Systems biology approach for mutational and site-specific structural investigation of DNA repair genes for xeroderma pigmentosum.
Xeroderma pigmentosum (XP) is a rare genetic skin disorder caused due to the extreme sensitivity for ultraviolet (UV) radiations. On its exposure, DNA acquires damages leading to skin and often neurological abnormalities. The DNA repair implicated in fixing UV-induced damages is NER and mutations in genes involved in NER and TLS form the basis of XP. The analyses of such mutations are vital for understanding XP and involved cancer genetics to facilitate the identification of crucial biomarkers and anticancer therapeutics. We detected the deleterious nsSNPs and examined them at structure-level by altering the structure, estimating secondary structure, solvent accessibility and performing site specific analysis. Crucial phosphorylation sites were also identified for their role in the disorder. These mutational and structural analyses offer valuable insight to the fundamental association of genetic mutations with phenotypic variations in XP and will assist experimental biologists to evaluate the mutations and their impact on genome.
Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology (JUIT), Waknaghat, Solan, H.P. 173234, India.
Manika
M
Sehgal
Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology (JUIT), Waknaghat, Solan, H.P. 173234, India. Electronic address: tiratharaj@gmail.com.
Tiratha Raj
TR
Singh
D004249:DNA Damage / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies / Q000379:methods; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation; D049490:Systems Biology / Q000379:methods*; D014983:Xeroderma Pigmentosum / Q000235:genetics*
C117669:DDB2 protein, human; D004268:DNA-Binding Proteins
Non-synonymous single nucleotide polymorphism; Nucleotide excision repair; Skin cancer; Structural variations; nsSNP