The structure of the human ERCC1/XPF interaction domains reveals a complementary role for the two proteins in nucleotide excision repair.
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.
Tripsianes
Konstantinos
K
Department of NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
Folkers
Gert
G
Ab
Eiso
E
Das
Devashish
D
Odijk
Hanny
H
Jaspers
Nicolaas G J
NG
Hoeijmakers
Jan H J
JH
Kaptein
Robert
R
Boelens
Rolf
R
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
D004268:DNA-Binding Proteins; C095888:xeroderma pigmentosum group F protein; D004247:DNA; C071447:ERCC1 protein, human; D004720:Endonucleases