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, Oct 04, 2015
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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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    • "The fission yeast shelterin-like complex also plays essential roles in protecting the ends of genomic DNAs from activation of the DNA damage checkpoint (Miyoshi et al. 2008; Palm and de Lange 2008; Moser and Nakamura 2009), although, paradoxically, it is widely accepted that the DNA damage sensor kinases are required for telomere maintenance (Lustig and Petes 1986; Metcalfe et al. 1996; Smilenov et al. 1997; Naito et al. 1998; Vespa et al. 2005; Moser et al. 2009). For example, in S. pombe, we previously reported that cells deleted of Tel1 and Rad3 had very short telomeres (Naito et al. 1998), suggesting that a downstream target of Tel1 and Rad3 operates to regulate telomere length, although the target has not yet been identified. "
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    ABSTRACT: In fission yeast, the DNA damage sensor kinases Tel1(ATM) and Rad3(ATR) exist at telomeres and are required for telomere maintenance, but the biological role they play at telomeres is not known. Here we show that the telomere protein Ccq1 is phosphorylated at Thr 93 (threonine residue at amino acid 93) by Tel1(ATM) and Rad3(ATR) both in vitro and in vivo. A ccq1 mutant in which alanine was substituted for Thr 93 failed to recruit telomerase to telomeres and showed gradual shortening of telomeres. These results indicate that the direct phosphorylation of Ccq1 Thr 93 by Tel1 and Rad3 is involved in the recruitment of telomerase to elongate telomeres.
    Genes & development 02/2012; 26(3):241-6. DOI:10.1101/gad.177873.111 · 10.80 Impact Factor
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