2rvb - Revision history

OCA at 07:06, 1 May 2024

2024-05-01T07:06:47Z

← Older revision		Revision as of 07:06, 1 May 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2rvb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RVB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RVB FirstGlance]. <br>		<table><tr><td colspan='2'>[[2rvb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RVB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RVB FirstGlance]. <br>
	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2rvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rvb OCA], [https://pdbe.org/2rvb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rvb RCSB], [https://www.ebi.ac.uk/pdbsum/2rvb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rvb ProSAT]</span></td></tr>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
			<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2rvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rvb OCA], [https://pdbe.org/2rvb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rvb RCSB], [https://www.ebi.ac.uk/pdbsum/2rvb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rvb ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 10:		Line 11:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/XPC_HUMAN XPC_HUMAN] Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex. Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides. This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity.<ref>PMID:9734359</ref> <ref>PMID:10734143</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:19609301</ref> <ref>PMID:19941824</ref> <ref>PMID:20649465</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref> The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1.<ref>PMID:9734359</ref> <ref>PMID:10734143</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:19609301</ref> <ref>PMID:19941824</ref> <ref>PMID:20649465</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref>		[https://www.uniprot.org/uniprot/XPC_HUMAN XPC_HUMAN] Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex. Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides. This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity.<ref>PMID:9734359</ref> <ref>PMID:10734143</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:19609301</ref> <ref>PMID:19941824</ref> <ref>PMID:20649465</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref> The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1.<ref>PMID:9734359</ref> <ref>PMID:10734143</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:19609301</ref> <ref>PMID:19941824</ref> <ref>PMID:20649465</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	In global genome repair (GGR), XPC detects damaged nucleotides and recruits TFIIH complex. The small acidic region of XPC binds to the pleckstrin homology (PH) domain of TFIIH subunit p62; however, the recognition mechanism remains elusive. Here, we use nuclear magnetic resonance to present the tertiary structure of XPC bound to the PH domain. The XPC acidic region forms a long string stabilized by insertion of Trp133 and Val136 into two separate hollows of the PH domain, coupled with extensive electrostatic contacts. Analysis of several XPC mutants revealed that particularly Trp133 is essential for binding to the PH domain. In cell lines stably expressing mutant XPC, alanine substitution at Trp133 or Trp133/Val136 compromised UV resistance, recruitment of TFIIH to DNA damage, and removal of UV-induced photoproducts from genomic DNA. These findings show how TFIIH complex is recruited by XPC to damaged DNA, advancing our understanding of the early stage of GGR.

	Structural Insight into the Mechanism of TFIIH Recognition by the Acidic String of the Nucleotide Excision Repair Factor XPC.,Okuda M, Kinoshita M, Kakumu E, Sugasawa K, Nishimura Y Structure. 2015 Aug 10. pii: S0969-2126(15)00290-7. doi:, 10.1016/j.str.2015.07.009. PMID:26278177<ref>PMID:26278177</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 2rvb" style="background-color:#fffaf0;"></div>~~
	== References ==		== References ==
	<references/>		<references/>

OCA at 20:53, 12 April 2023

2023-04-12T20:53:54Z

← Older revision		Revision as of 20:53, 12 April 2023
Line 1:		Line 1:

	==Solution structure of the complex between XPC acidic domain and TFIIH p62 PH domain==		==Solution structure of the complex between XPC acidic domain and TFIIH p62 PH domain==
	<StructureSection load='2rvb' size='340' side='right'caption='[[2rvb~~]], [[NMR_Ensembles_of_Models \| 20 NMR models~~]]' scene=''>		<StructureSection load='2rvb' size='340' side='right'caption='[[2rvb]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2rvb]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RVB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RVB FirstGlance]. <br>		<table><tr><td colspan='2'>[[2rvb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RVB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RVB FirstGlance]. <br>
	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2rvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rvb OCA], [https://pdbe.org/2rvb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rvb RCSB], [https://www.ebi.ac.uk/pdbsum/2rvb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rvb ProSAT]</span></td></tr>		</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2rvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rvb OCA], [https://pdbe.org/2rvb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rvb RCSB], [https://www.ebi.ac.uk/pdbsum/2rvb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rvb ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/XPC_HUMAN XPC_HUMAN]] Defects in XPC are a cause of xeroderma pigmentosum complementation group C (XP-C) [MIM:[https://omim.org/entry/278720 278720]]; also known as xeroderma pigmentosum III (XP3). XP-C is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities.<ref>PMID:19609301</ref> <ref>PMID:17682058</ref> <ref>PMID:17355181</ref> <ref>PMID:8298653</ref> <ref>PMID:10766188</ref>		[https://www.uniprot.org/uniprot/XPC_HUMAN XPC_HUMAN] Defects in XPC are a cause of xeroderma pigmentosum complementation group C (XP-C) [MIM:[https://omim.org/entry/278720 278720]; also known as xeroderma pigmentosum III (XP3). XP-C is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities.<ref>PMID:19609301</ref> <ref>PMID:17682058</ref> <ref>PMID:17355181</ref> <ref>PMID:8298653</ref> <ref>PMID:10766188</ref>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/XPC_HUMAN XPC_HUMAN]] Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex. Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides. This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity.<ref>PMID:9734359</ref> <ref>PMID:10734143</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:19609301</ref> <ref>PMID:19941824</ref> <ref>PMID:20649465</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref> The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1.<ref>PMID:9734359</ref> <ref>PMID:10734143</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:19609301</ref> <ref>PMID:19941824</ref> <ref>PMID:20649465</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref> [[https://www.uniprot.org/uniprot/TF2H1_HUMAN TF2H1_HUMAN]] Component of the core-TFIIH basal transcription factor involved in nucleotide excision repair (NER) of DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II.		[https://www.uniprot.org/uniprot/XPC_HUMAN XPC_HUMAN] Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex. Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides. This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity.<ref>PMID:9734359</ref> <ref>PMID:10734143</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:19609301</ref> <ref>PMID:19941824</ref> <ref>PMID:20649465</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref> The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1.<ref>PMID:9734359</ref> <ref>PMID:10734143</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:19609301</ref> <ref>PMID:19941824</ref> <ref>PMID:20649465</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Nishimura, Y]]		[[Category: Nishimura Y]]
	[[Category: Okuda, M]]		[[Category: Okuda M]]
	~~[[Category: Acidic domain]]~~
	~~[[Category: Dna binding protein-transcription complex]]~~
	~~[[Category: Dna repair]]~~
	~~[[Category: General transcription factor]]~~
	~~[[Category: Human tfiih p62]]~~
	~~[[Category: Human xpc]]~~
	~~[[Category: Ph domain~~]]

OCA at 10:37, 7 July 2021

2021-07-07T10:37:29Z

← Older revision		Revision as of 10:37, 7 July 2021
Line 3:		Line 3:
	<StructureSection load='2rvb' size='340' side='right'caption='[[2rvb]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>		<StructureSection load='2rvb' size='340' side='right'caption='[[2rvb]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2rvb]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RVB OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2RVB FirstGlance]. <br>		<table><tr><td colspan='2'>[[2rvb]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RVB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RVB FirstGlance]. <br>
	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2rvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rvb OCA], [~~http~~://pdbe.org/2rvb PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2rvb RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2rvb PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2rvb ProSAT]</span></td></tr>		</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2rvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rvb OCA], [https://pdbe.org/2rvb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rvb RCSB], [https://www.ebi.ac.uk/pdbsum/2rvb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rvb ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/XPC_HUMAN XPC_HUMAN]] Defects in XPC are a cause of xeroderma pigmentosum complementation group C (XP-C) [MIM:[~~http~~://omim.org/entry/278720 278720]]; also known as xeroderma pigmentosum III (XP3). XP-C is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities.<ref>PMID:19609301</ref> <ref>PMID:17682058</ref> <ref>PMID:17355181</ref> <ref>PMID:8298653</ref> <ref>PMID:10766188</ref>		[[https://www.uniprot.org/uniprot/XPC_HUMAN XPC_HUMAN]] Defects in XPC are a cause of xeroderma pigmentosum complementation group C (XP-C) [MIM:[https://omim.org/entry/278720 278720]]; also known as xeroderma pigmentosum III (XP3). XP-C is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities.<ref>PMID:19609301</ref> <ref>PMID:17682058</ref> <ref>PMID:17355181</ref> <ref>PMID:8298653</ref> <ref>PMID:10766188</ref>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/XPC_HUMAN XPC_HUMAN]] Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex. Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides. This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity.<ref>PMID:9734359</ref> <ref>PMID:10734143</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:19609301</ref> <ref>PMID:19941824</ref> <ref>PMID:20649465</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref> The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1.<ref>PMID:9734359</ref> <ref>PMID:10734143</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:19609301</ref> <ref>PMID:19941824</ref> <ref>PMID:20649465</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref> [[~~http~~://www.uniprot.org/uniprot/TF2H1_HUMAN TF2H1_HUMAN]] Component of the core-TFIIH basal transcription factor involved in nucleotide excision repair (NER) of DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II.		[[https://www.uniprot.org/uniprot/XPC_HUMAN XPC_HUMAN]] Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex. Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides. This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity.<ref>PMID:9734359</ref> <ref>PMID:10734143</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:19609301</ref> <ref>PMID:19941824</ref> <ref>PMID:20649465</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref> The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1.<ref>PMID:9734359</ref> <ref>PMID:10734143</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:19609301</ref> <ref>PMID:19941824</ref> <ref>PMID:20649465</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref> [[https://www.uniprot.org/uniprot/TF2H1_HUMAN TF2H1_HUMAN]] Component of the core-TFIIH basal transcription factor involved in nucleotide excision repair (NER) of DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 07:35, 21 August 2019

2019-08-21T07:35:05Z

← Older revision		Revision as of 07:35, 21 August 2019
Line 1:		Line 1:

	==Solution structure of the complex between XPC acidic domain and TFIIH p62 PH domain==		==Solution structure of the complex between XPC acidic domain and TFIIH p62 PH domain==
	<StructureSection load='2rvb' size='340' side='right' caption='[[2rvb]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>		<StructureSection load='2rvb' size='340' side='right'caption='[[2rvb]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2rvb]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RVB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RVB FirstGlance]. <br>		<table><tr><td colspan='2'>[[2rvb]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RVB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RVB FirstGlance]. <br>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Large Structures]]
	[[Category: Nishimura, Y]]		[[Category: Nishimura, Y]]
	[[Category: Okuda, M]]		[[Category: Okuda, M]]

OCA at 09:24, 3 August 2017

2017-08-03T09:24:17Z

← Older revision		Revision as of 09:24, 3 August 2017
Line 1:		Line 1:

	==Solution structure of the complex between XPC acidic domain and TFIIH p62 PH domain==		==Solution structure of the complex between XPC acidic domain and TFIIH p62 PH domain==
	<StructureSection load='2rvb' size='340' side='right' caption='[[2rvb]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>		<StructureSection load='2rvb' size='340' side='right' caption='[[2rvb]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2rvb]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RVB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RVB FirstGlance]. <br>		<table><tr><td colspan='2'>[[2rvb]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RVB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RVB FirstGlance]. <br>
	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2rvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rvb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2rvb RCSB], [http://www.ebi.ac.uk/pdbsum/2rvb PDBsum]</span></td></tr>		</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2rvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rvb OCA], [http://pdbe.org/2rvb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rvb RCSB], [http://www.ebi.ac.uk/pdbsum/2rvb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2rvb ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 17:		Line 18:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 2rvb" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 11:13, 9 September 2015

2015-09-09T11:13:04Z

← Older revision		Revision as of 11:13, 9 September 2015
Line 1:		Line 1:
	'''~~Unreleased~~ structure'''		==Solution structure of the complex between XPC acidic domain and TFIIH p62 PH domain==
			<StructureSection load='2rvb' size='340' side='right' caption='[[2rvb]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[2rvb]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RVB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RVB FirstGlance]. <br>
			</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2rvb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rvb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2rvb RCSB], [http://www.ebi.ac.uk/pdbsum/2rvb PDBsum]</span></td></tr>
			</table>
			== Disease ==
			[[http://www.uniprot.org/uniprot/XPC_HUMAN XPC_HUMAN]] Defects in XPC are a cause of xeroderma pigmentosum complementation group C (XP-C) [MIM:[http://omim.org/entry/278720 278720]]; also known as xeroderma pigmentosum III (XP3). XP-C is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities.<ref>PMID:19609301</ref> <ref>PMID:17682058</ref> <ref>PMID:17355181</ref> <ref>PMID:8298653</ref> <ref>PMID:10766188</ref>
			== Function ==
			[[http://www.uniprot.org/uniprot/XPC_HUMAN XPC_HUMAN]] Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex. Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides. This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity.<ref>PMID:9734359</ref> <ref>PMID:10734143</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:19609301</ref> <ref>PMID:19941824</ref> <ref>PMID:20649465</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref> The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1.<ref>PMID:9734359</ref> <ref>PMID:10734143</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:19609301</ref> <ref>PMID:19941824</ref> <ref>PMID:20649465</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref> [[http://www.uniprot.org/uniprot/TF2H1_HUMAN TF2H1_HUMAN]] Component of the core-TFIIH basal transcription factor involved in nucleotide excision repair (NER) of DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			In global genome repair (GGR), XPC detects damaged nucleotides and recruits TFIIH complex. The small acidic region of XPC binds to the pleckstrin homology (PH) domain of TFIIH subunit p62; however, the recognition mechanism remains elusive. Here, we use nuclear magnetic resonance to present the tertiary structure of XPC bound to the PH domain. The XPC acidic region forms a long string stabilized by insertion of Trp133 and Val136 into two separate hollows of the PH domain, coupled with extensive electrostatic contacts. Analysis of several XPC mutants revealed that particularly Trp133 is essential for binding to the PH domain. In cell lines stably expressing mutant XPC, alanine substitution at Trp133 or Trp133/Val136 compromised UV resistance, recruitment of TFIIH to DNA damage, and removal of UV-induced photoproducts from genomic DNA. These findings show how TFIIH complex is recruited by XPC to damaged DNA, advancing our understanding of the early stage of GGR.

	~~The entry 2rvb is ON HOLD until Paper Publication~~		Structural Insight into the Mechanism of TFIIH Recognition by the Acidic String of the Nucleotide Excision Repair Factor XPC.,Okuda M, Kinoshita M, Kakumu E, Sugasawa K, Nishimura Y Structure. 2015 Aug 10. pii: S0969-2126(15)00290-7. doi:, 10.1016/j.str.2015.07.009. PMID:26278177<ref>PMID:26278177</ref>

	~~Authors: Okuda~~, M.~~, Nishimura, Y~~.		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	~~Description: Solution structure of the complex between XPC acidic domain and TFIIH p62 PH domain~~		== References ==
	~~[[Category: Unreleased Structures]]~~		<references/>
			__TOC__
			</StructureSection>
	[[Category: Nishimura, Y]]		[[Category: Nishimura, Y]]
	[[Category: Okuda, M]]		[[Category: Okuda, M]]
			[[Category: Acidic domain]]
			[[Category: Dna binding protein-transcription complex]]
			[[Category: Dna repair]]
			[[Category: General transcription factor]]
			[[Category: Human tfiih p62]]
			[[Category: Human xpc]]
			[[Category: Ph domain]]

OCA at 08:59, 29 July 2015

2015-07-29T08:59:04Z

← Older revision		Revision as of 08:59, 29 July 2015
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 2rvb is ON HOLD		The entry 2rvb is ON HOLD until Paper Publication

	Authors: Okuda, M., Nishimura, Y.		Authors: Okuda, M., Nishimura, Y.

OCA: Protected "2rvb" [edit=sysop:move=sysop]

2015-07-08T09:26:02Z

Protected "2rvb" [edit=sysop:move=sysop]

← Older revision	Revision as of 09:26, 8 July 2015
(No difference)

OCA: New page: '''Unreleased structure''' The entry 2rvb is ON HOLD Authors: Okuda, M., Nishimura, Y. Description: Solution structure of the complex between XPC acidic domain and TFIIH p62 PH domain ...

2015-07-08T09:26:01Z

New page: '''Unreleased structure''' The entry 2rvb is ON HOLD Authors: Okuda, M., Nishimura, Y. Description: Solution structure of the complex between XPC acidic domain and TFIIH p62 PH domain ...

New page

'''Unreleased structure'''

The entry 2rvb is ON HOLD

Authors: Okuda, M., Nishimura, Y.

Description: Solution structure of the complex between XPC acidic domain and TFIIH p62 PH domain
[[Category: Unreleased Structures]]
[[Category: Nishimura, Y]]
[[Category: Okuda, M]]