Telomerase in Space and Time: Regulation of Yeast Telomerase Function at Telomeres and DNA Breaks

Vasianovich, Yulia; Krallis, Alexandra; Wellinger, Raymund J.

doi:10.5772/intechopen.85750

Cited by 2 publications

(3 citation statements)

References 149 publications

(330 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, fission yeast devoid of the two major DDR kinases also behave like telomerase-negative cells ( Naito et al, 1998 ; Nakamura et al, 2002 ). These results demonstrate that activity of DDR kinases is necessary to properly maintain telomeric ends, likely by allowing appropriate processing of telomeres, i.e., post-replicative end processing and telomerase activation and/or recruitment [more details on the link between DDR kinases and appropriate processing of telomeres can be found in these reviews ( Doksani and de Lange, 2014 ; Vasianovich et al, 2019 )]. These results suggest also that recognition of telomeres as DNA damage (in a controlled manner) is a prerequisite to genome stability.…”

Section: Telomeric Dna Replication By the Conventional Replication Mamentioning

confidence: 90%

Telomere Replication: Solving Multiple End Replication Problems

Bonnell

Pasquier

Wellinger

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Eukaryotic genomes are highly complex and divided into linear chromosomes that require end protection from unwarranted fusions, recombination, and degradation in order to maintain genomic stability. This is accomplished through the conserved specialized nucleoprotein structure of telomeres. Due to the repetitive nature of telomeric DNA, and the unusual terminal structure, namely a protruding single stranded 3′ DNA end, completing telomeric DNA replication in a timely and efficient manner is a challenge. For example, the end replication problem causes a progressive shortening of telomeric DNA at each round of DNA replication, thus telomeres eventually lose their protective capacity. This phenomenon is counteracted by the recruitment and the activation at telomeres of the specialized reverse transcriptase telomerase. Despite the importance of telomerase in providing a mechanism for complete replication of telomeric ends, the majority of telomere replication is in fact carried out by the conventional DNA replication machinery. There is significant evidence demonstrating that progression of replication forks is hampered at chromosomal ends due to telomeric sequences prone to form secondary structures, tightly DNA-bound proteins, and the heterochromatic nature of telomeres. The telomeric loop (t-loop) formed by invasion of the 3′-end into telomeric duplex sequences may also impede the passage of replication fork. Replication fork stalling can lead to fork collapse and DNA breaks, a major cause of genomic instability triggered notably by unwanted repair events. Moreover, at chromosomal ends, unreplicated DNA distal to a stalled fork cannot be rescued by a fork coming from the opposite direction. This highlights the importance of the multiple mechanisms involved in overcoming fork progression obstacles at telomeres. Consequently, numerous factors participate in efficient telomeric DNA duplication by preventing replication fork stalling or promoting the restart of a stalled replication fork at telomeres. In this review, we will discuss difficulties associated with the passage of the replication fork through telomeres in both fission and budding yeasts as well as mammals, highlighting conserved mechanisms implicated in maintaining telomere integrity during replication, thus preserving a stable genome.

show abstract

Section: Telomeric Dna Replication By the Conventional Replication Mamentioning

confidence: 90%

Telomere Replication: Solving Multiple End Replication Problems

Bonnell

Pasquier

Wellinger

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…This Sir4-mediated recruitment of telomerase to sites near telomeres may also serve to prevent telomerase association with DNA double-strand breaks, and thus block inappropriate healing of such sites by de novo telomere addition. Consistent with this idea, DNA break repair and telomere elongation appear to occur in different nuclear sub-compartments (Kramer and Haber 1993 ; Gartenberg 2009 ; Vasianovich et al 2019 ). It must be noted that in principle, telomerase-mediated telomere elongation can occur in G1, but on normal telomeres, the presence of Rif1 and Rif2 prevents such events (Gallardo et al 2011 ).…”

Section: Tlc1 Association With Telomerase Proteins and Recruitment To Telomeresmentioning

confidence: 83%

“…Est2-Tlc1 form the minimal catalytic core of the enzyme, associating with Est1 and Est3 only at specific stages of the cell cycle, which may serve as a regulatory mechanism, restricting the time of telomerase function at telomeres (Fig. 1 , step 5; Tucey and Lundblad 2014 ; Vasianovich et al 2019 ). In addition, there is evidence of Est2 dissociation and telomerase disassembly after telomere elongation in late S/G2 phase (Tucey and Lundblad 2014 ).…”

Section: Tlc1 Association With Telomerase Proteins and Recruitment To Telomeresmentioning

confidence: 99%

Maturation and shuttling of the yeast telomerase RNP: assembling something new using recycled parts

2021

Self Cite

View full text Add to dashboard Cite

As the limiting component of the budding yeast telomerase, the Tlc1 RNA must undergo multiple consecutive modifications and rigorous quality checks throughout its lifecycle. These steps will ensure that only correctly processed and matured molecules are assembled into telomerase complexes that subsequently act at telomeres. The complex pathway of Tlc1 RNA maturation, involving 5'- and 3'-end processing, stabilisation and assembly with the protein subunits, requires at least one nucleo-cytoplasmic passage. Furthermore, it appears that the pathway is tightly coordinated with the association of various and changing proteins, including the export factor Xpo1, the Mex67/Mtr2 complex, the Kap122 importin, the Sm7 ring and possibly the CBC and TREX-1 complexes. Although many of these maturation processes also affect other RNA species, the Tlc1 RNA exploits them in a new combination and, therefore, ultimately follows its own and unique pathway. In this review, we highlight recent new insights in maturation and subcellular shuttling of the budding yeast telomerase RNA and discuss how these events may be fine-tuned by the biochemical characteristics of the varying processing and transport factors as well as the final telomerase components. Finally, we indicate outstanding questions that we feel are important to be addressed for a complete understanding of the telomerase RNA lifecycle and that could have implications for the human telomerase as well.

show abstract

Telomerase in Space and Time: Regulation of Yeast Telomerase Function at Telomeres and DNA Breaks

Cited by 2 publications

References 149 publications

Telomere Replication: Solving Multiple End Replication Problems

Telomere Replication: Solving Multiple End Replication Problems

Maturation and shuttling of the yeast telomerase RNP: assembling something new using recycled parts

Contact Info

Product

Resources

About