title: The structure of the human ERCC1/XPF interaction domains reveals a complementary role for the two proteins in nucleotide excision repair.
abstract: The human ERCC1/XPF complex is a structure-specific endonuclease with defined polarity that participates in multiple DNA repair pathways. We report the heterodimeric structure of the C-terminal domains of both proteins responsible for ERCC1/XPF complex formation. Both domains exhibit the double helix-hairpin-helix motif (HhH)2, and they are related by a pseudo-2-fold symmetry axis. In the XPF domain, the hairpin of the second motif is replaced by a short turn. The ERCC1 domain folds properly only in the presence of the XPF domain, which implies a role for XPF as a scaffold for the folding of ERCC1. The intersubunit interactions are largely hydrophobic in nature. NMR titration data show that only the ERCC1 domain of the ERCC1/XPF complex is involved in DNA binding. On the basis of these findings, we propose a model for the targeting of XPF nuclease via ERCC1-mediated interactions in the context of nucleotide excision repair.
authors.affiliation: Department of NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tripsianes
authors.forename: Gert
authors.initials: G
authors.lastname: Folkers
authors.forename: Eiso
authors.initials: E
authors.lastname: Ab
authors.forename: Devashish
authors.initials: D
authors.lastname: Das
authors.forename: Hanny
authors.initials: H
authors.lastname: Odijk
authors.forename: Nicolaas G J
authors.initials: NG
authors.lastname: Jaspers
authors.forename: Jan H J
authors.initials: JH
authors.lastname: Hoeijmakers
authors.forename: Robert
authors.initials: R
authors.lastname: Kaptein
authors.forename: Rolf
authors.initials: R
authors.lastname: Boelens
mesh_terms: D000595:Amino Acid Sequence; D004247:DNA / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D019281:Dimerization; D004720:Endonucleases / Q000737:chemistry* / Q000502:physiology; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D008969:Molecular Sequence Data; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary
chemical_list: D004268:DNA-Binding Proteins; C095888:xeroderma pigmentosum group F protein; D004247:DNA; C071447:ERCC1 protein, human; D004720:Endonucleases