Xeroderma Pigmentosum Group C Protein Complex Is the Initiator of Global Genome Nucleotide Excision Repair
The XPC-HR23B complex is specifically involved in global genome but not transcription-coupled nucleotide excision repair (NER). Its function is unknown. Using a novel DNA damage recognition-competition assay, we identified XPC-HR23B as the earliest damage detector to initiate NER: it acts before the...
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| Veröffentlicht in: | Molecular cell 1998-08, Vol.2 (2), p.223-232 |
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| creator | Sugasawa, Kaoru Ng, Jessica M.Y Masutani, Chikahide Iwai, Shigenori van der Spek, Peter J Eker, André P.M Hanaoka, Fumio Bootsma, Dirk Hoeijmakers, Jan H.J |
| description | The XPC-HR23B complex is specifically involved in global genome but not transcription-coupled nucleotide excision repair (NER). Its function is unknown. Using a novel DNA damage recognition-competition assay, we identified XPC-HR23B as the earliest damage detector to initiate NER: it acts before the known damage-binding protein XPA. Coimmunoprecipitation and DNase I footprinting show that XPC-HR23B binds to a variety of NER lesions. These results resolve the function of XPC-HR23B, define the first NER stages, and suggest a two-step mechanism of damage recognition involving damage detection by XPC-HR23B followed by damage verification by XPA. This provides a plausible explanation for the extreme damage specificity exhibited by global genome repair. In analogy, in the transcription-coupled NER subpathway, RNA polymerase II may take the role of XPC. After this subpathway-specific initial lesion detection, XPA may function as a common damage verifier and adaptor to the core of the NER apparatus. |
| doi_str_mv | 10.1016/S1097-2765(00)80132-X |
| format | Article |
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Its function is unknown. Using a novel DNA damage recognition-competition assay, we identified XPC-HR23B as the earliest damage detector to initiate NER: it acts before the known damage-binding protein XPA. Coimmunoprecipitation and DNase I footprinting show that XPC-HR23B binds to a variety of NER lesions. These results resolve the function of XPC-HR23B, define the first NER stages, and suggest a two-step mechanism of damage recognition involving damage detection by XPC-HR23B followed by damage verification by XPA. This provides a plausible explanation for the extreme damage specificity exhibited by global genome repair. In analogy, in the transcription-coupled NER subpathway, RNA polymerase II may take the role of XPC. After this subpathway-specific initial lesion detection, XPA may function as a common damage verifier and adaptor to the core of the NER apparatus.</description><subject>Base Sequence</subject><subject>Binding, Competitive</subject><subject>DNA - genetics</subject><subject>DNA - metabolism</subject><subject>DNA Damage</subject><subject>DNA Repair</subject><subject>DNA-Binding Proteins - chemistry</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Genome, Human</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Macromolecular Substances</subject><subject>Models, Biological</subject><subject>Xeroderma Pigmentosum - genetics</subject><subject>Xeroderma Pigmentosum - metabolism</subject><subject>Xeroderma Pigmentosum Group A Protein</subject><issn>1097-2765</issn><issn>1097-4164</issn><issn>1097-4164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1v1DAUtBBVaQs_oZJPiB4Cz7GdxCeEVmVZqaJVC9LeLK_9DK6SONgOKv---yWuPb2nNzNvpBlCLhl8ZMCaTw8MVFvVbSM_AFx1wHhdrV-Rs_1ZsEa8Pu47yhtynvMjABOyU6fkVLVccKnOyOMaU3SYBkPvwq8BxxLzPNBlivNEF_QuxYJhpIs4TD0-0VWm5TfS1RhKMCUmGj1d9nFjerrEMQ5Iv8-2x1iCQ3r9ZEMOcaT3OJmQ3pITb_qM747zgvz8ev1j8a26uV2uFl9uKisUlIobLr30wLBxbYeuc14iAycVKi8bxS3fSKlEixJqL1pWgwdfG3TQeSE5vyDvD3-nFP_MmIseQrbY92bEOGfd8q5RUjQvElkjGxB7ojwQbYo5J_R6SmEw6Z9moHdl6H0Zepe0BtD7MvR6q7s8GsybAd1_1TH9Lf75gOM2jr8Bk8424GjRhYS2aBfDCw7Py9yZxg</recordid><startdate>19980801</startdate><enddate>19980801</enddate><creator>Sugasawa, Kaoru</creator><creator>Ng, Jessica M.Y</creator><creator>Masutani, Chikahide</creator><creator>Iwai, Shigenori</creator><creator>van der Spek, Peter J</creator><creator>Eker, André P.M</creator><creator>Hanaoka, Fumio</creator><creator>Bootsma, Dirk</creator><creator>Hoeijmakers, Jan H.J</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7X8</scope></search><sort><creationdate>19980801</creationdate><title>Xeroderma Pigmentosum Group C Protein Complex Is the Initiator of Global Genome Nucleotide Excision Repair</title><author>Sugasawa, Kaoru ; Ng, Jessica M.Y ; Masutani, Chikahide ; Iwai, Shigenori ; van der Spek, Peter J ; Eker, André P.M ; Hanaoka, Fumio ; Bootsma, Dirk ; Hoeijmakers, Jan H.J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-3a35f5f01e6d78ed8df5e10d59e9f5693c3b55947e502f47120f0f2aed08f4533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Base Sequence</topic><topic>Binding, Competitive</topic><topic>DNA - genetics</topic><topic>DNA - metabolism</topic><topic>DNA Damage</topic><topic>DNA Repair</topic><topic>DNA-Binding Proteins - chemistry</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Genome, Human</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Macromolecular Substances</topic><topic>Models, Biological</topic><topic>Xeroderma Pigmentosum - genetics</topic><topic>Xeroderma Pigmentosum - metabolism</topic><topic>Xeroderma Pigmentosum Group A Protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sugasawa, Kaoru</creatorcontrib><creatorcontrib>Ng, Jessica M.Y</creatorcontrib><creatorcontrib>Masutani, Chikahide</creatorcontrib><creatorcontrib>Iwai, Shigenori</creatorcontrib><creatorcontrib>van der Spek, Peter J</creatorcontrib><creatorcontrib>Eker, André P.M</creatorcontrib><creatorcontrib>Hanaoka, Fumio</creatorcontrib><creatorcontrib>Bootsma, Dirk</creatorcontrib><creatorcontrib>Hoeijmakers, Jan H.J</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sugasawa, Kaoru</au><au>Ng, Jessica M.Y</au><au>Masutani, Chikahide</au><au>Iwai, Shigenori</au><au>van der Spek, Peter J</au><au>Eker, André P.M</au><au>Hanaoka, Fumio</au><au>Bootsma, Dirk</au><au>Hoeijmakers, Jan H.J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Xeroderma Pigmentosum Group C Protein Complex Is the Initiator of Global Genome Nucleotide Excision Repair</atitle><jtitle>Molecular cell</jtitle><addtitle>Mol Cell</addtitle><date>1998-08-01</date><risdate>1998</risdate><volume>2</volume><issue>2</issue><spage>223</spage><epage>232</epage><pages>223-232</pages><issn>1097-2765</issn><issn>1097-4164</issn><eissn>1097-4164</eissn><abstract>The XPC-HR23B complex is specifically involved in global genome but not transcription-coupled nucleotide excision repair (NER). Its function is unknown. Using a novel DNA damage recognition-competition assay, we identified XPC-HR23B as the earliest damage detector to initiate NER: it acts before the known damage-binding protein XPA. Coimmunoprecipitation and DNase I footprinting show that XPC-HR23B binds to a variety of NER lesions. These results resolve the function of XPC-HR23B, define the first NER stages, and suggest a two-step mechanism of damage recognition involving damage detection by XPC-HR23B followed by damage verification by XPA. This provides a plausible explanation for the extreme damage specificity exhibited by global genome repair. In analogy, in the transcription-coupled NER subpathway, RNA polymerase II may take the role of XPC. 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| subjects | Base Sequence Binding, Competitive DNA - genetics DNA - metabolism DNA Damage DNA Repair DNA-Binding Proteins - chemistry DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Genome, Human Humans In Vitro Techniques Macromolecular Substances Models, Biological Xeroderma Pigmentosum - genetics Xeroderma Pigmentosum - metabolism Xeroderma Pigmentosum Group A Protein |
| title | Xeroderma Pigmentosum Group C Protein Complex Is the Initiator of Global Genome Nucleotide Excision Repair |
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