spRap1 and spRif1, recruited to telomeres by Taz1, are essential for telomere function in fission yeast

Abstract

Telomeres are essential for genome integrity. scRap1 (S. cerevisiae Rap1) directly binds to telomeric DNA and regulates telomere length and telomere position effect (TPE) by recruiting two different groups of proteins to its RCT (Rap1 C-terminal) domain. The first group, Rif1 and Rif2, regulates telomere length. The second group, Sir3 and Sir4, is involved in heterochromatin formation. On the other hand, human TRF1 and TRF2, as well as their fission yeast homolog, Taz1, directly bind to telomeric DNA and negatively regulate telomere length. Taz1 also plays important roles in TPE and meiosis. Human Rap1, the ortholog of scRap1, negatively regulates telomere length and appears to be recruited to telomeres by interacting with TRF2. Here, we describe two novel fission yeast proteins, spRap1 (S. pombe Rap1) and spRif1 (S. pombe Rif1), which are orthologous to scRap1 and scRif1, respectively. spRap1 and spRif1 are independently recruited to telomeres by interacting with Taz1. The rap1 mutant is severely defective in telomere length control, TPE, and telomere clustering toward the spindle pole body (SPB) at the premeiotic horsetail stage, indicating that spRap1 has critical roles in these telomere functions. The rif1 mutant also shows some defects in telomere length control and meiosis. Our results indicate that Taz1 provides binding sites for telomere regulators, spRap1 and spRif1, which perform the essential telomere functions. This study establishes the similarity of telomere organization in fission yeast and humans.

Fission yeast telomere-binding protein Taz1 is a functional but not a structural counterpart of human TRF1 and TRF2

“…Fission yeast Schizosaccharomyces pombe (S. pombe) Taz1 associates with telomeric dsDNAs and plays an important role in telomere length regulation and protection [6,[8][9][10][11][12]. In addition, similar to TRF1 and TRF2, Taz1 also negatively regulates telomere length via a "protein-counting" mechanism by recruiting Rap1 and Rif1 [9,12]. Therefore, Taz1 has been considered as the functional ortholog of mammalian TRF proteins.…”

Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly

“…The ability of shelterin to regulate telomeric heterochromatin is key to bypassing RNAi One of the common phenotypes of the telomere-related mutants that bypass RNAi is that they all affect telomere silencing (Cooper et al 1997;Nimmo et al 1998;Kanoh and Ishikawa 2001;Sugiyama et al 2007;Moser et al 2009). However, the mechanism by which shelterin nucleates heterochromatin assembly is unknown.…”

Conservation and evolvability in regulatory networks: The evolution of ribosomal regulation in yeast

“…Thus, whereas the DNA binding domains of Rap1p (Myb-domains) have been conserved in all species, the TA domain, which is responsible for Rap1p's role as an RP transcription factor (17), follows exactly the same evolutionary pattern as the RAP1 binding site in RP promoters and is present only in the clade spanning from A. gossypii to S. cerevisiae. Moreover, Rap1p from species lacking the TA domain, such as C. albicans and S. pombe, cannot functionally complement for the S. cerevisiae Rap1p (18)(19)(20), whereas those with the TA domain (e.g., S. castellii) are adequate substitutes (21). Thus, the acquired domain allowed Rap1p to assume a novel role in transcriptional regulation, whereas its conserved DNA binding domain determined the sequence of its corresponding cis-element.…”