Abstract
Human XPF/ERCC1 is a structure-specific DNA endonuclease that nicks the damaged DNA strand at the 5' end during nucleotide excision repair. We determined the structure of the complex of the C-terminal domain of XPF with 10 nt ssDNA. A positively charged region within the second helix of the first HhH motif contacts the ssDNA phosphate backbone. One guanine base is flipped out of register and positioned in a pocket contacting residues from both HhH motifs of XPF. Comparison to other HhH-containing proteins indicates a one-residue deletion in the second HhH motif of XPF that has altered the hairpin conformation, thereby permitting ssDNA interactions. Previous nuclear magnetic resonance studies showed that ERCC1 in the XPF-ERCC1 heterodimer can bind dsDNA. Combining the two observations gives a model that underscores the asymmetry of the human XPF/ERCC1 heterodimer in binding at an ss/ds DNA junction.
Original language | English |
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Pages (from-to) | 667-75 |
Number of pages | 9 |
Journal | Structure |
Volume | 20 |
Issue number | 4 |
DOIs | |
Publication status | Published - 4 Apr 2012 |
Keywords
- Amino Acid Motifs
- Binding Sites
- DNA
- DNA Repair
- DNA, Single-Stranded
- DNA-Binding Proteins
- Endonucleases
- Guanine
- Humans
- Magnetic Resonance Spectroscopy
- Models, Molecular
- Mutation
- Protein Binding
- Protein Multimerization
- Protein Structure, Secondary
- Recombinant Proteins
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
- Static Electricity
- Journal Article
- Research Support, Non-U.S. Gov't