title: Comparative insight into nucleotide excision repair components of Plasmodium falciparum.
abstract: Nucleotide excision repair (NER) is one of the DNA repair pathways crucial for maintenance of genome integrity and deals with repair of DNA damages arising due to exogenous and endogenous factors. The multi-protein transcription initiation factor TFIIH plays a critical role in NER and transcription and is highly conserved throughout evolution. The malaria parasite Plasmodium falciparum has been a challenge for the researchers for a long time because of emergence of drug resistance. The availability of its genome sequence has opened new avenues for research. Antimalarial drugs like chloroquine and mefloquine have been reported to inhibit NER pathway mediated repair reactions and thus promote mutagenesis. Previous studies have validated existence and implied possible association of defective or altered DNA repair pathways with development of drug resistant phenotype in certain P. falciparum strains. We conjecture that a compromised NER pathway in combination with other DNA repair pathways might be conducive for the emergence and sustenance of drug resistance in P. falciparum. Therefore we decided to unravel the components of NER pathway in P. falciparum and using bioinformatics based approaches here we report a genome wide in silico analysis of NER components from P. falciparum and their comparison with the human host. Our results reveal that P. falciparum genome contains almost all the components of NER but we were unable to find clear homologue for p62 and XPC in its genome. The structure modeling of all the components further suggests that their structures are significantly conserved. Furthermore this study lays a foundation to perform similar comparative studies between drug resistant and drug sensitive strains of parasite in order to understand DNA repair-related mechanisms of drug resistance.
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology, P.O. Box 10504, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Leila
authors.initials: L
authors.lastname: Tajedin
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology, P.O. Box 10504, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Masroor
authors.initials: M
authors.lastname: Anwar
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology, P.O. Box 10504, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Gupta
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology, P.O. Box 10504, Aruna Asaf Ali Marg, New Delhi 110067, India. Electronic address: renututeja@gmail.com.
authors.forename: Renu
authors.initials: R
authors.lastname: Tuteja
mesh_terms: D000595:Amino Acid Sequence; D000962:Antimalarials / Q000494:pharmacology; D004260:DNA Repair / Q000235:genetics*; D004351:Drug Resistance; D017125:Genes, Protozoan; D023281:Genomics; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D000962:Antimalarials; D015800:Protozoan Proteins
keywords: DNA repair; Helicase; Malaria parasite; Plasmodium falciparum; Unwinding