A novel Rap1p-interacting factor, Rif2p, cooperates with Rif1p to regulate telomere length in Saccharomyces cerevisiae.
David Wotton,David Shore +1 more
TL;DR: The results suggest that telomere length regulation is mediated by a protein complex consisting of Rif1p and Rif2p, each of which has distinct regulatory functions.
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Abstract: The Saccharomyces cerevisiae Rap1 protein binds with high affinity to sites within the poly(C(1-3)A) tracts at telomeres, where it plays a role in both telomere length regulation and the initiation of telomeric silencing. Rap1p initiates silencing at telomeres by interacting through its carboxy-terminal domain with Sir3p and Sir4p, both of which are required for repression. This same domain of Rap1p also negatively regulates telomere elongation, through an unknown mechanism. We have identified a new Rap1-interacting factor (Rif2p) that plays a role in telomere length regulation. Rif2p has considerable functional similarities with a Rap1p-interacting factor (Rif1p) identified previously. Mutations in RIF1 or RIF2 (unlike mutations in the silencing genes SIR3 and SIR4) result in moderate telomere elongation and improved telomeric silencing. However, deletion of both RIF1 and RIF2 in the same cell results in a dramatic increase in telomere length, similar to that seen with a carboxy-terminal truncation of Rap1p. In addition, overexpression of either RIF1 or RIF2 decreases telomere length, and co-overexpression of these proteins can reverse the telomere elongation effect of overexpression of the Rap1p carboxyl terminus. Finally, we show that Rif1p and Rif2p can interact with each other in vivo. These results suggest that telomere length regulation is mediated by a protein complex consisting of Rif1p and Rif2p, each of which has distinct regulatory functions. One role of Rap1p in telomere length regulation is to recruit these proteins to the telomeres.
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References
Modifiers of position effect are shared between telomeric and silent mating-type loci in S. cerevisiae.
TL;DR: In this article, SIR2, SIR3, NAT1, ARD1, and HHF2 (histone H4) were identified as modifiers of the position effect at telomeres in S. cerevisiae.
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Evidence that a complex of sir proteins interacts with the silencer and telomere-binding protein rap1
TL;DR: It is proposed that RAP1 acts in the initiation of transcriptional silencing by recruiting a complex of SIR proteins to the chromosome via protein-protein interactions and is consistent with a model in which SIR3 and SIR4 play a structural role in the maintenance of silent chromatin.
A RAP1-interacting protein involved in transcriptional silencing and telomere length regulation.
TL;DR: The two-hybrid system is used to suggest that RIF1 is a cofactor or mediator for RAP1 in the establishment of a repressed chromatin state at these loci and support the idea that the rap1s phenotypes are attributable to a failure to recruit Rif1 to silencers and telomeres.
The saccharomyces PIF1 DNA helicase inhibits telomere elongation and de novo telomere formation
TL;DR: Results suggest that the PIF1 helicase is an inhibitor of both de novo telomere formation and telomeres elongation in pif1 mutants.
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The Saccharomyces CDC13 protein is a single-strand TG1–3 telomeric DNA-binding protein in vitro that affects telomere behavior in vivo
Jing-Jer Lin,Virginia A. Zakian +1 more
TL;DR: The data suggest that Cdc13p functions by binding directly to telomeric DNA, thereby limiting its accessibility to degradation and transcription as well as masking it from factors that detect damaged DNA.
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