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| | <StructureSection load='5nw5' size='340' side='right'caption='[[5nw5]], [[Resolution|resolution]] 6.50Å' scene=''> | | <StructureSection load='5nw5' size='340' side='right'caption='[[5nw5]], [[Resolution|resolution]] 6.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5nw5]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NW5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NW5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5nw5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NW5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NW5 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5nvr|5nvr]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 6.502Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RIF1, YBR275C, YBR1743 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</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=5nw5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nw5 OCA], [https://pdbe.org/5nw5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nw5 RCSB], [https://www.ebi.ac.uk/pdbsum/5nw5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nw5 ProSAT]</span></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=5nw5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nw5 OCA], [http://pdbe.org/5nw5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nw5 RCSB], [http://www.ebi.ac.uk/pdbsum/5nw5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nw5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RIF1_YEAST RIF1_YEAST]] Negatively regulates telomere length by preventing telomere elongation or promoting degradation of the telomere ends. Recruited to telomeres by interaction with the C-terminus of RAP1, which binds directly to telomeric repeat DNA. This may create a negative feedback loop in which the addition of new telomere repeats creates binding sites for inhibitors of telomere length extension. May also influence the balance of transcriptional silencing at telomeres and the silent mating type locus HMR, which is mediated by SIR (Silent Information Regulator) proteins including SIR3 and SIR4. RIF1 competes with SIR proteins for binding to the C-terminus of RAP1. In the absence of RIF1, a limiting cellular pool of SIR proteins may preferentially associate with RAP1 at sub-telomeric loci, causing enhanced telomeric silencing and attenuated silencing of the HMR locus.<ref>PMID:1577274</ref> <ref>PMID:7867933</ref> <ref>PMID:9087429</ref> <ref>PMID:10531008</ref> <ref>PMID:15572688</ref> | + | [https://www.uniprot.org/uniprot/RIF1_YEAST RIF1_YEAST] Negatively regulates telomere length by preventing telomere elongation or promoting degradation of the telomere ends. Recruited to telomeres by interaction with the C-terminus of RAP1, which binds directly to telomeric repeat DNA. This may create a negative feedback loop in which the addition of new telomere repeats creates binding sites for inhibitors of telomere length extension. May also influence the balance of transcriptional silencing at telomeres and the silent mating type locus HMR, which is mediated by SIR (Silent Information Regulator) proteins including SIR3 and SIR4. RIF1 competes with SIR proteins for binding to the C-terminus of RAP1. In the absence of RIF1, a limiting cellular pool of SIR proteins may preferentially associate with RAP1 at sub-telomeric loci, causing enhanced telomeric silencing and attenuated silencing of the HMR locus.<ref>PMID:1577274</ref> <ref>PMID:7867933</ref> <ref>PMID:9087429</ref> <ref>PMID:10531008</ref> <ref>PMID:15572688</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Baker's yeast]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bunker, R D]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Reinert, J K]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Shi, T]] | + | [[Category: Bunker RD]] |
| - | [[Category: Thoma, N H]] | + | [[Category: Reinert JK]] |
| - | [[Category: All-alpha fold]] | + | [[Category: Shi T]] |
| - | [[Category: Dna binding protein]] | + | [[Category: Thoma NH]] |
| - | [[Category: Dna double-strand break repair]]
| + | |
| - | [[Category: Irregular helical repeat]]
| + | |
| - | [[Category: Telomere maintenance]]
| + | |
| Structural highlights
Function
RIF1_YEAST Negatively regulates telomere length by preventing telomere elongation or promoting degradation of the telomere ends. Recruited to telomeres by interaction with the C-terminus of RAP1, which binds directly to telomeric repeat DNA. This may create a negative feedback loop in which the addition of new telomere repeats creates binding sites for inhibitors of telomere length extension. May also influence the balance of transcriptional silencing at telomeres and the silent mating type locus HMR, which is mediated by SIR (Silent Information Regulator) proteins including SIR3 and SIR4. RIF1 competes with SIR proteins for binding to the C-terminus of RAP1. In the absence of RIF1, a limiting cellular pool of SIR proteins may preferentially associate with RAP1 at sub-telomeric loci, causing enhanced telomeric silencing and attenuated silencing of the HMR locus.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
In yeast, Rif1 is part of the telosome, where it inhibits telomerase and checkpoint signaling at chromosome ends. In mammalian cells, Rif1 is not telomeric, but it suppresses DNA end resection at chromosomal breaks, promoting repair by nonhomologous end joining (NHEJ). Here, we describe crystal structures for the uncharacterized and conserved approximately 125-kDa N-terminal domain of Rif1 from Saccharomyces cerevisiae (Rif1-NTD), revealing an alpha-helical fold shaped like a shepherd's crook. We identify a high-affinity DNA-binding site in the Rif1-NTD that fully encases DNA as a head-to-tail dimer. Engagement of the Rif1-NTD with telomeres proved essential for checkpoint control and telomere length regulation. Unexpectedly, Rif1-NTD also promoted NHEJ at DNA breaks in yeast, revealing a conserved role of Rif1 in DNA repair. We propose that tight associations between the Rif1-NTD and DNA gate access of processing factors to DNA ends, enabling Rif1 to mediate diverse telomere maintenance and DNA repair functions.
Rif1 maintains telomeres and mediates DNA repair by encasing DNA ends.,Mattarocci S, Reinert JK, Bunker RD, Fontana GA, Shi T, Klein D, Cavadini S, Faty M, Shyian M, Hafner L, Shore D, Thoma NH, Rass U Nat Struct Mol Biol. 2017 Jul;24(7):588-595. doi: 10.1038/nsmb.3420. Epub 2017, Jun 12. PMID:28604726[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hardy CF, Sussel L, Shore D. A RAP1-interacting protein involved in transcriptional silencing and telomere length regulation. Genes Dev. 1992 May;6(5):801-14. PMID:1577274
- ↑ Buck SW, Shore D. Action of a RAP1 carboxy-terminal silencing domain reveals an underlying competition between HMR and telomeres in yeast. Genes Dev. 1995 Feb 1;9(3):370-84. PMID:7867933
- ↑ Wotton D, Shore D. A novel Rap1p-interacting factor, Rif2p, cooperates with Rif1p to regulate telomere length in Saccharomyces cerevisiae. Genes Dev. 1997 Mar 15;11(6):748-60. PMID:9087429
- ↑ Mishra K, Shore D. Yeast Ku protein plays a direct role in telomeric silencing and counteracts inhibition by rif proteins. Curr Biol. 1999 Oct 7;9(19):1123-6. PMID:10531008
- ↑ Levy DL, Blackburn EH. Counting of Rif1p and Rif2p on Saccharomyces cerevisiae telomeres regulates telomere length. Mol Cell Biol. 2004 Dec;24(24):10857-67. PMID:15572688 doi:10.1128/MCB.24.24.10857-10867.2004
- ↑ Mattarocci S, Reinert JK, Bunker RD, Fontana GA, Shi T, Klein D, Cavadini S, Faty M, Shyian M, Hafner L, Shore D, Thoma NH, Rass U. Rif1 maintains telomeres and mediates DNA repair by encasing DNA ends. Nat Struct Mol Biol. 2017 Jul;24(7):588-595. doi: 10.1038/nsmb.3420. Epub 2017, Jun 12. PMID:28604726 doi:http://dx.doi.org/10.1038/nsmb.3420
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