|
|
| (3 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Structure of FACT_subnucleosome complex 2== | | ==Structure of FACT_subnucleosome complex 2== |
| - | <StructureSection load='6upl' size='340' side='right'caption='[[6upl]], [[Resolution|resolution]] 7.40Å' scene=''> | + | <SX load='6upl' size='340' side='right' viewer='molstar' caption='[[6upl]], [[Resolution|resolution]] 7.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6upl]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UPL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UPL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6upl]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UPL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UPL FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 7.4Å</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=6upl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6upl OCA], [http://pdbe.org/6upl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6upl RCSB], [http://www.ebi.ac.uk/pdbsum/6upl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6upl ProSAT]</span></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=6upl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6upl OCA], [https://pdbe.org/6upl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6upl RCSB], [https://www.ebi.ac.uk/pdbsum/6upl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6upl ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/H2A1C_HUMAN H2A1C_HUMAN]] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. | + | [https://www.uniprot.org/uniprot/SSRP1_HUMAN SSRP1_HUMAN] Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II. The FACT complex is probably also involved in phosphorylation of 'Ser-392' of p53/TP53 via its association with CK2 (casein kinase II). Binds specifically to double-stranded DNA and at low levels to DNA modified by the antitumor agent cisplatin. May potentiate cisplatin-induced cell death by blocking replication and repair of modified DNA. Also acts as a transcriptional coactivator for p63/TP63.<ref>PMID:9489704</ref> <ref>PMID:9566881</ref> <ref>PMID:9836642</ref> <ref>PMID:10912001</ref> <ref>PMID:11239457</ref> <ref>PMID:12374749</ref> <ref>PMID:12934006</ref> <ref>PMID:16713563</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The organization of genomic DNA into nucleosomes profoundly affects all DNA-related processes in eukaryotes. The histone chaperone 'FAcilitates Chromatin Transcription' (FACT; consisting of subunits SPT16 and SSRP1(1)) promotes both disassembly and reassembly of nucleosomes during gene transcription, DNA replication, and repair(2). The mechanism by which FACT causes these opposing outcomes is unknown. Here we report two cryo-EM structures of human FACT in complex with partially assembled sub-nucleosomes, with supporting biochemical and hydrogen-deuterium exchange (HDX) data. FACT is engaged in extensive interactions with nucleosomal DNA and all histones. The large DNA-binding surface on FACT appears to be protected by the C-terminal domains of both subunits, and this inhibition is released by interaction with H2A-H2B, allowing FACT-H2A-H2B to dock onto a (H3-H4)2-DNA complex(3). SPT16 binds nucleosomal DNA and tethers H2A-H2B through its C-terminal domain by acting as a placeholder for DNA. SSRP1 also contributes to DNA binding, and can assume two conformations, depending on whether a second H2A-H2B dimer is present. Our data suggest a compelling mechanism for how FACT maintains chromatin integrity during polymerase passage, by facilitating H2A-H2B dimer removal, stabilizing intermediate 'sub-nucleosomal' states, and promoting nucleosome reassembly. Our findings reconcile discrepancies regarding the many roles of FACT and underscore the dynamic interactions between histone chaperones and nucleosomes.
| + | |
| | | | |
| - | FACT caught in the act of manipulating the nucleosome.,Liu Y, Zhou K, Zhang N, Wei H, Tan YZ, Zhang Z, Carragher B, Potter CS, D'Arcy S, Luger K Nature. 2019 Nov 27. pii: 10.1038/s41586-019-1820-0. doi:, 10.1038/s41586-019-1820-0. PMID:31775157<ref>PMID:31775157</ref>
| + | ==See Also== |
| - | | + | *[[Histone 3D structures|Histone 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6upl" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| - | </StructureSection> | + | </SX> |
| | + | [[Category: Escherichia coli]] |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Carragher, B]] | + | [[Category: Carragher B]] |
| - | [[Category: Liu, Y]] | + | [[Category: Liu Y]] |
| - | [[Category: Luger, K]] | + | [[Category: Luger K]] |
| - | [[Category: Potter, C]] | + | [[Category: Potter C]] |
| - | [[Category: Tan, Y Z]] | + | [[Category: Tan YZ]] |
| - | [[Category: Wei, H]] | + | [[Category: Wei H]] |
| - | [[Category: Zhou, K]] | + | [[Category: Zhou K]] |
| - | [[Category: Histone chaperone]]
| + | |
| - | [[Category: Integrity]]
| + | |
| - | [[Category: Nucleosome assembly]]
| + | |
| - | [[Category: Nucleosome disassembly]]
| + | |
| - | [[Category: Replication]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription-dna complex]]
| + | |
| - | [[Category: Transient]]
| + | |
| Structural highlights
Function
SSRP1_HUMAN Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II. The FACT complex is probably also involved in phosphorylation of 'Ser-392' of p53/TP53 via its association with CK2 (casein kinase II). Binds specifically to double-stranded DNA and at low levels to DNA modified by the antitumor agent cisplatin. May potentiate cisplatin-induced cell death by blocking replication and repair of modified DNA. Also acts as a transcriptional coactivator for p63/TP63.[1] [2] [3] [4] [5] [6] [7] [8]
See Also
References
- ↑ Orphanides G, LeRoy G, Chang CH, Luse DS, Reinberg D. FACT, a factor that facilitates transcript elongation through nucleosomes. Cell. 1998 Jan 9;92(1):105-16. PMID:9489704
- ↑ Dyer MA, Hayes PJ, Baron MH. The HMG domain protein SSRP1/PREIIBF is involved in activation of the human embryonic beta-like globin gene. Mol Cell Biol. 1998 May;18(5):2617-28. PMID:9566881
- ↑ LeRoy G, Orphanides G, Lane WS, Reinberg D. Requirement of RSF and FACT for transcription of chromatin templates in vitro. Science. 1998 Dec 4;282(5395):1900-4. PMID:9836642
- ↑ Wada T, Orphanides G, Hasegawa J, Kim DK, Shima D, Yamaguchi Y, Fukuda A, Hisatake K, Oh S, Reinberg D, Handa H. FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH. Mol Cell. 2000 Jun;5(6):1067-72. PMID:10912001
- ↑ Keller DM, Zeng X, Wang Y, Zhang QH, Kapoor M, Shu H, Goodman R, Lozano G, Zhao Y, Lu H. A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1. Mol Cell. 2001 Feb;7(2):283-92. PMID:11239457
- ↑ Zeng SX, Dai MS, Keller DM, Lu H. SSRP1 functions as a co-activator of the transcriptional activator p63. EMBO J. 2002 Oct 15;21(20):5487-97. PMID:12374749
- ↑ Belotserkovskaya R, Oh S, Bondarenko VA, Orphanides G, Studitsky VM, Reinberg D. FACT facilitates transcription-dependent nucleosome alteration. Science. 2003 Aug 22;301(5636):1090-3. PMID:12934006 doi:http://dx.doi.org/10.1126/science.1085703
- ↑ Pavri R, Zhu B, Li G, Trojer P, Mandal S, Shilatifard A, Reinberg D. Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II. Cell. 2006 May 19;125(4):703-17. PMID:16713563 doi:http://dx.doi.org/S0092-8674(06)00570-8
|
