Crystal structure of the FeS cluster-containing nucleotide excision repair helicase XPD.
DNA damage recognition by the nucleotide excision repair pathway requires an initial step identifying helical distortions in the DNA and a proofreading step verifying the presence of a lesion. This proofreading step is accomplished in eukaryotes by the TFIIH complex. The critical damage recognition...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2008-06-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.0060149&type=printable |
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| author | Stefanie C Wolski Jochen Kuper Petra Hänzelmann James J Truglio Deborah L Croteau Bennett Van Houten Caroline Kisker |
| author_facet | Stefanie C Wolski Jochen Kuper Petra Hänzelmann James J Truglio Deborah L Croteau Bennett Van Houten Caroline Kisker |
| author_sort | Stefanie C Wolski |
| collection | DOAJ |
| description | DNA damage recognition by the nucleotide excision repair pathway requires an initial step identifying helical distortions in the DNA and a proofreading step verifying the presence of a lesion. This proofreading step is accomplished in eukaryotes by the TFIIH complex. The critical damage recognition component of TFIIH is the XPD protein, a DNA helicase that unwinds DNA and identifies the damage. Here, we describe the crystal structure of an archaeal XPD protein with high sequence identity to the human XPD protein that reveals how the structural helicase framework is combined with additional elements for strand separation and DNA scanning. Two RecA-like helicase domains are complemented by a 4Fe4S cluster domain, which has been implicated in damage recognition, and an alpha-helical domain. The first helicase domain together with the helical and 4Fe4S-cluster-containing domains form a central hole with a diameter sufficient in size to allow passage of a single stranded DNA. Based on our results, we suggest a model of how DNA is bound to the XPD protein, and can rationalize several of the mutations in the human XPD gene that lead to one of three severe diseases, xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. |
| format | Article |
| id | doaj-art-47c1567275b9428db74dcd5e17c8f7df |
| institution | OA Journals |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2008-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-47c1567275b9428db74dcd5e17c8f7df2025-08-20T02:00:50ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852008-06-0166e14910.1371/journal.pbio.0060149Crystal structure of the FeS cluster-containing nucleotide excision repair helicase XPD.Stefanie C WolskiJochen KuperPetra HänzelmannJames J TruglioDeborah L CroteauBennett Van HoutenCaroline KiskerDNA damage recognition by the nucleotide excision repair pathway requires an initial step identifying helical distortions in the DNA and a proofreading step verifying the presence of a lesion. This proofreading step is accomplished in eukaryotes by the TFIIH complex. The critical damage recognition component of TFIIH is the XPD protein, a DNA helicase that unwinds DNA and identifies the damage. Here, we describe the crystal structure of an archaeal XPD protein with high sequence identity to the human XPD protein that reveals how the structural helicase framework is combined with additional elements for strand separation and DNA scanning. Two RecA-like helicase domains are complemented by a 4Fe4S cluster domain, which has been implicated in damage recognition, and an alpha-helical domain. The first helicase domain together with the helical and 4Fe4S-cluster-containing domains form a central hole with a diameter sufficient in size to allow passage of a single stranded DNA. Based on our results, we suggest a model of how DNA is bound to the XPD protein, and can rationalize several of the mutations in the human XPD gene that lead to one of three severe diseases, xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.0060149&type=printable |
| spellingShingle | Stefanie C Wolski Jochen Kuper Petra Hänzelmann James J Truglio Deborah L Croteau Bennett Van Houten Caroline Kisker Crystal structure of the FeS cluster-containing nucleotide excision repair helicase XPD. PLoS Biology |
| title | Crystal structure of the FeS cluster-containing nucleotide excision repair helicase XPD. |
| title_full | Crystal structure of the FeS cluster-containing nucleotide excision repair helicase XPD. |
| title_fullStr | Crystal structure of the FeS cluster-containing nucleotide excision repair helicase XPD. |
| title_full_unstemmed | Crystal structure of the FeS cluster-containing nucleotide excision repair helicase XPD. |
| title_short | Crystal structure of the FeS cluster-containing nucleotide excision repair helicase XPD. |
| title_sort | crystal structure of the fes cluster containing nucleotide excision repair helicase xpd |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.0060149&type=printable |
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