title: Unraveling DNA repair in human: molecular mechanisms and consequences of repair defect.
abstract: Cellular genomes are vulnerable to an array of DNA-damaging agents, of both endogenous and environmental origin. Such damage occurs at a frequency too high to be compatible with life. As a result cell death and tissue degeneration, aging and cancer are caused. To avoid this and in order for the genome to be reproduced, these damages must be corrected efficiently by DNA repair mechanisms. Eukaryotic cells have multiple mechanisms for the repair of damaged DNA. These repair systems in humans protect the genome by repairing modified bases, DNA adducts, crosslinks and double-strand breaks. The lesions in DNA are eliminated by mechanisms such as direct reversal, base excision and nucleotide excision. The base excision repair eliminates single damaged-base residues by the action of specialized DNA glycosylases and AP endonucleases. Nucleotide excision repair excises damage within oligomers that are 25 to 32 nucleotides long. This repair utilizes many proteins to remove the major UV-induced photoproducts from DNA, as well as other types of modified nucleotides. Different DNA polymerases and ligases are utilized to complete the separate pathways. The double-strand breaks in DNA are repaired by mechanisms that involve DNA protein kinase and recombination proteins. The defect in one of the repair protein results in three rare recessive syndromes: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. This review describes the biochemistry of various repair processes and summarizes the clinical features and molecular mechanisms underlying these disorders.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India.
authors.forename: N
authors.initials: N
authors.lastname: Tuteja
authors.forename: R
authors.initials: R
authors.lastname: Tuteja
mesh_terms: D000478:Alkylation; D000818:Animals; D001260:Ataxia Telangiectasia / Q000201:enzymology / Q000235:genetics; D020137:Base Pair Mismatch; D019757:Carbon-Oxygen Lyases / Q000502:physiology; D019457:Chromosome Breakage; D002873:Chromosome Fragility / Q000235:genetics; D003057:Cockayne Syndrome / Q000201:enzymology / Q000235:genetics; D003432:Cross-Linking Reagents / Q000633:toxicity; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D018736:DNA Adducts; D004249:DNA Damage; D045647:DNA Glycosylases; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics / Q000502:physiology; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D043223:Deoxyribonuclease IV (Phage T4-Induced); D004720:Endonucleases; D005544:Forecasting; D005808:Genes, Recessive; D005816:Genetic Complementation Test; D020022:Genetic Predisposition to Disease; D006201:Hair Diseases / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000201:enzymology / Q000235:genetics; D008322:Mammals / Q000235:genetics / Q000378:metabolism; D009699:N-Glycosyl Hydrolases / Q000502:physiology; D009260:Nail Diseases / Q000201:enzymology / Q000235:genetics; D009369:Neoplasms / Q000209:etiology / Q000235:genetics; D009687:Nuclear Proteins; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000502:physiology; D010777:Photochemistry; D010787:Photosensitivity Disorders / Q000201:enzymology / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000502:physiology; D011740:Pyrimidine Dimers / Q000378:metabolism; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000502:physiology; D019473:Transcription Factors, TFII; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000201:enzymology / Q000235:genetics; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D019757:Carbon-Oxygen Lyases; D003432:Cross-Linking Reagents; D004247:DNA; D018736:DNA Adducts; D045647:DNA Glycosylases; D004265:DNA Helicases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D043223:Deoxyribonuclease IV (Phage T4-Induced); D004720:Endonucleases; D009699:N-Glycosyl Hydrolases; D009687:Nuclear Proteins; D019853:O(6)-Methylguanine-DNA Methyltransferase; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011740:Pyrimidine Dimers; D051758:Transcription Factor TFIIH; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5; C497263:PRKDC protein, human; C071447:ERCC1 protein, human; C497292:ERCC2 protein, human