PMID:10946233
| Citation |
Morikawa, K and Shirakawa, M (2000) Three-dimensional structural views of damaged-DNA recognition: T4 endonuclease V, E. coli Vsr protein, and human nucleotide excision repair factor XPA. Mutat. Res. 460:257-75 |
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| Abstract |
Genetic information is frequently disturbed by introduction of modified or mismatch bases into duplex DNA, and hence all organisms contain DNA repair systems to restore normal genetic information by removing such damaged bases or nucleotides and replacing them by correct ones. The understanding of this repair mechanism is a central subject in cell biology. This review focuses on the three-dimensional structural views of damaged DNA recognition by three proteins. The first protein is T4 endonuclease V (T4 endo V), which catalyzes the first reaction step of the excision repair pathway to remove pyrimidine-dimers (PD) produced within duplex DNA by UV irradiation. The crystal structure of this enzyme complexed with DNA containing a thymidine-dimer provided the first direct view of DNA lesion recognition by a repair enzyme, indicating that the DNA kink coupled with base flipping-out is important for damaged DNA recognition. The second is very short patch repair (Vsr) endonuclease, which recognizes a TG mismatch within the five base pair consensus sequence. The crystal structure of this enzyme in complex with duplex DNA containing a TG mismatch revealed a novel mismatch base pair recognition scheme, where three aromatic residues intercalate from the major groove into the DNA to strikingly deform the base pair stacking but the base flipping-out does not occur. The third is human nucleotide excision repair (NER) factor XPA, which is a major component of a large protein complex. This protein has been shown to bind preferentially to UV- or chemical carcinogen-damaged DNA. The solution structure of the XPA central domain, essential for the interaction of damaged DNA, was determined by NMR. This domain was found to be divided mainly into a (Cys)4-type zinc-finger motif subdomain for replication protein A (RPA) recognition and the carboxyl terminal subdomain responsible for DNA binding. |
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| Keywords |
Amino Acid Motifs; Amino Acid Sequence; Base Pair Mismatch; Binding Sites; Catalysis; DNA/chemistry; DNA/metabolism; DNA Damage; DNA Repair; DNA, Bacterial/chemistry; DNA, Bacterial/metabolism; DNA, Bacterial/radiation effects; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/metabolism; Deoxyribonuclease (Pyrimidine Dimer); Endodeoxyribonucleases/chemistry; Endodeoxyribonucleases/metabolism; Helix-Turn-Helix Motifs; Humans; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Sequence Data; Nucleic Acid Conformation; Protein Binding; Protein Conformation; Protein Structure, Tertiary; Pyrimidine Dimers/chemistry; Pyrimidine Dimers/metabolism; Replication Protein A; Sequence Alignment; Sequence Homology, Amino Acid; Structure-Activity Relationship; Substrate Specificity; Ultraviolet Rays; Viral Proteins; Xeroderma Pigmentosum Group A Protein |
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