TY - JOUR
T1 - The structure of the human ERCC1/XPF interaction domains reveals a complementary role for the two proteins in nucleotide excision repair
AU - Tripsianes, Konstantinos
AU - Folkers, Gert
AU - Ab, Eiso
AU - Das, Devashish
AU - Odijk, Hanny
AU - Jaspers, Nicolaas G.J.
AU - Hoeijmakers, Jan H.J.
AU - Kaptein, Robert
AU - Boelens, Rolf
N1 - Funding Information:
The authors are grateful to Dr. Tammo Diercks for expert NMR assistance. This work was financially supported by the Research Council for the Chemical Sciences of the Netherlands Organization for Scientific Research (NWO-CW) and by the Center for Biomedical Genetics. H.O., N.G.J.J., and J.H.J.H. were supported by Euratom grants nrs FIGH-CT-2002-00207 and LSHG-CT-2005-512113.
PY - 2005/12
Y1 - 2005/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/28844480409
U2 - 10.1016/j.str.2005.08.014
DO - 10.1016/j.str.2005.08.014
M3 - Article
C2 - 16338413
AN - SCOPUS:28844480409
SN - 0969-2126
VL - 13
SP - 1849
EP - 1858
JO - Structure
JF - Structure
IS - 12
ER -