Protection and replication of telomeres in fission yeast

Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 900 S. Ashland Ave. MC669, Chicago, IL 60607, USA.
Biochemistry and Cell Biology (Impact Factor: 2.15). 10/2009; 87(5):747-58. DOI: 10.1139/O09-037
Source: PubMed


Telomeres, the natural ends of linear chromosomes, must be protected and completely replicated to guarantee genomic stability in eukaryotic cells. However, the protected state of telomeres is not compatible with recruitment of telomerase, an enzyme responsible for extending telomeric G-rich repeats during S-phase; thus, telomeres must undergo switches from a protected state to an accessible state during the cell cycle. In this minireview, we will summarize recent advances in our understanding of proteins involved in the protection and replication of telomeres, and the way these factors are dynamically recruited to telomeres during the cell cycle. We will focus mainly on recent results from fission yeast Schizosaccharomyces pombe, and compare them with results from budding yeast Saccharomyces cerevisiae and mammalian cell studies. In addition, a model for the way in which fission yeast cells replicate telomeres will be presented.

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Available from: Toru M Nakamura,
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    • "Therefore, the interaction between the proteins TPP1 and TIN2 forms the keystone of the bridge between ss-DNA and ds-DNA. A similar organization is found in the terminal Schizosaccharomyces pombe complex that also contains six proteins (reviewed in Moser and Nakamura, 2009). "
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    ABSTRACT: A major issue in telomere research is to understand how the integrity of chromosome ends is controlled. The fact that different types of nucleoprotein complexes have been described at the telomeres of different organisms raises the question of whether they have in common a structural identity that explains their role in chromosome protection. We will review here how telomeric nucleoprotein complexes are structured, comparing different organisms and trying to link these structures to telomere biology. It emerges that telomeres are formed by a complex and specific network of interactions between DNA, RNA, and proteins. The fact that these interactions and associated activities are reinforcing each other might help to guarantee the robustness of telomeric functions across the cell cycle and in the event of cellular perturbations. We will also discuss the recent notion that telomeres have evolved specific systems to overcome the DNA topological stress generated during their replication and transcription. This will lead to revisit the way we envisage the functioning of telomeric complexes since the regulation of topology is central to DNA stability, replication, recombination, and transcription as well as to chromosome higher-order organization.
    Frontiers in Oncology 03/2013; 3:48. DOI:10.3389/fonc.2013.00048
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    • "Heterochromatin formation has an important function also for telomere capping in Schizosaccharomyces pombe. In this organism , telomere protection is assured by a complex of shelterinlike proteins (Moser and Nakamura, 2009). In the absence of telomerase, S. pombe cells can survive telomere loss by adopting an alternative mode to protect chromosome ends based on amplification and rearrangement of heterochromatic regions (Jain et al., 2010). "
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    ABSTRACT: The establishment of a specific nucleoprotein structure, the telomere, is required to ensure the protection of chromosome ends from being recognized as DNA damage sites. Telomere shortening below a critical length triggers a DNA damage response that leads to replicative senescence. In normal human somatic cells, characterized by telomere shortening with each cell division, telomere uncapping is a regulated process associated with cell turnover. Nevertheless, telomere dysfunction has also been associated with genomic instability, cell transformation, and cancer. Despite the essential role telomeres play in chromosome protection and in tumorigenesis, our knowledge of the chromatin structure involved in telomere maintenance is still limited. Here we review the recent findings on chromatin modifications associated with the dynamic changes of telomeres from protected to deprotected state and their role in telomere functions.
    Frontiers in Oncology 03/2013; 3:46. DOI:10.3389/fonc.2013.00046
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    • "This review aims to describe the unique and shared features of telomerases from ciliates, yeasts, and vertebrates with an emphasis on pathways of telomerase RNA biogenesis and RNP assembly. Telomerase physical recruitment to, elongation of, and regulation at telomeres are modulated by dynamic telomeric chromatin reviewed extensively elsewhere (Stern and Bryan 2008; Moser and Nakamura 2009; Schoeftner and Blasco 2009; de Lange 2010; Stewart et al. 2012). Most telomerase studies have involved Tetrahymena thermophila, Saccharomyces cerevisiae, Schizosaccharomyces pombe, mice, or cultured human cells. "
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    ABSTRACT: Telomerase adds simple-sequence repeats to the ends of linear chromosomes to counteract the loss of end sequence inherent in conventional DNA replication. Catalytic activity for repeat synthesis results from the cooperation of the telomerase reverse transcriptase protein (TERT) and the template-containing telomerase RNA (TER). TERs vary widely in sequence and structure but share a set of motifs required for TERT binding and catalytic activity. Species-specific TER motifs play essential roles in RNP biogenesis, stability, trafficking, and regulation. Remarkably, the biogenesis pathways that generate mature TER differ across eukaryotes. Furthermore, the cellular processes that direct the assembly of a biologically functional telomerase holoenzyme and its engagement with telomeres are evolutionarily varied and regulated. This review highlights the diversity of strategies for telomerase RNP biogenesis, RNP assembly, and telomere recruitment among ciliates, yeasts, and vertebrates and suggests common themes in these pathways and their regulation.
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