4bjt

Structural highlights

Function

[RAP1_YEAST] Essential regulatory protein in yeast whose DNA-binding sites are found at three types of chromosomal elements: promoters, silencers, and telomeres. RAP1 is also involved in the regulation of telomere structure, where its binding sites are found within the terminal poly[C(1-3)A] sequences. The opposite regulatory functions of RAP1 are not intrinsic to its binding sites but, instead, result from interactions with different factors at promoters and silencers. RAP1 associates with SIR3 and SIR4 proteins to form a DNA-binding complex that initiates the repression at the HM loci and telomeres. May also target the binding of RIF1 and RIF2 to silencers and telomeres. Forms with GCR1 a transcriptional activation complex that is required for expression of glycolytic and ribosomal gene. [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]}

References

1. ↑ 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
2. ↑ 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
3. ↑ 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
4. ↑ 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
5. ↑ 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
6. ↑ Shi T, Bunker RD, Mattarocci S, Ribeyre C, Faty M, Gut H, Scrima A, Rass U, Rubin SM, Shore D, Thoma NH. Rif1 and Rif2 Shape Telomere Function and Architecture through Multivalent Rap1 Interactions. Cell. 2013 Jun 6;153(6):1340-53. doi: 10.1016/j.cell.2013.05.007. PMID:23746845 doi:10.1016/j.cell.2013.05.007