Telomere recombination pathways: tales of several unhappy marriages

Lue, Neal F.; Yu, Eun Young

doi:10.1007/s00294-016-0653-8

Cited by 19 publications

(17 citation statements)

References 71 publications

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“…In addition, the invariably telomeric location of the active VSG would facilitate the DNA rearrangements mediating VSG switching. DNA recombination reactions at telomeres mediate the generation of sequence diversity within polymorphic gene families involved in phenotypic or antigenic variation which are frequently telomeric (Keely et al ., ; Scherf et al ., ; de Las Penas et al ., ; Lue and Yu, ). In T. brucei this is also the case, and the telomeric VSG can be switched either through telomere exchange or through gene conversions (Li, ; McCulloch et al ., ).…”

Section: Discussionmentioning

confidence: 99%

The role of genomic location and flanking 3′UTR in the generation of functional levels of variant surface glycoprotein in Trypanosoma brucei

Ridewood

Ooi

Hall

et al. 2017

Molecular Microbiology

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Summary Trypanosoma brucei faces relentless immune attack in the mammalian bloodstream, where it is protected by an essential coat of Variant Surface Glycoprotein (VSG) comprising ∼10% total protein. The active VSG gene is in a Pol I‐transcribed telomeric expression site (ES). We investigated factors mediating these extremely high levels of VSG expression by inserting ectopic VSG117 into VSG221 expressing T. brucei. Mutational analysis of the ectopic VSG 3′UTR demonstrated the essentiality of a conserved 16‐mer for mRNA stability. Expressing ectopic VSG117 from different genomic locations showed that functional VSG levels could be produced from a gene 60 kb upstream of its normal telomeric location. High, but very heterogeneous levels of VSG117 were obtained from the Pol I‐transcribed rDNA. Blocking VSG synthesis normally triggers a precise precytokinesis cell‐cycle checkpoint. VSG117 expression from the rDNA was not adequate for functional complementation, and the stalled cells arrested prior to cytokinesis. However, VSG levels were not consistently low enough to trigger a characteristic ‘VSG synthesis block’ cell‐cycle checkpoint, as some cells reinitiated S phase. This demonstrates the essentiality of a Pol I‐transcribed ES, as well as conserved VSG 3′UTR 16‐mer sequences for the generation of functional levels of VSG expression in bloodstream form T. brucei.

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Section: Discussionmentioning

confidence: 99%

The role of genomic location and flanking 3′UTR in the generation of functional levels of variant surface glycoprotein in Trypanosoma brucei

Ridewood

Ooi

Hall

et al. 2017

Molecular Microbiology

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“…Sir-mediated chromatin structure could also participate to telomere capping and limit resection at the terminal TG repeats protecting telomere from unwanted recombination events (Lue and Yu 2017).…”

Section: Limiting Resection In Heterochromatin: What Functional Consementioning

confidence: 99%

Keep moving and stay in a good shape to find your homologous recombination partner

Bordelet

Dubrana

2018

Curr Genet

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Genomic DNA is constantly exposed to damage. Among the lesion in DNA, double-strand breaks (DSB), because they disrupt the two strands of the DNA double helix, are the more dangerous. DSB are repaired through two evolutionary conserved mechanisms: Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR). Whereas NHEJ simply reseals the double helix with no or minimal processing, HR necessitates the formation of a 3′ssDNA through the processing of DSB ends by the resection machinery and relies on the recognition and pairing of this 3′ssDNA tails with an intact homologous sequence. Despite years of active research on HR, the manner by which the two homologous sequences find each other in the crowded nucleus, and how this modulates HR efficiency, only recently emerges. Here, we review recent advances in our understanding of the factors limiting the search of a homologous sequence during HR.

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“…We termed them non-terminal arrests and showed that they were, at least partially, Mec1-and Pol32-dependent. Combined with evidence that recombination factors such as Rad51 and Rad52 are important for cell growth not only as an alternative telomere maintenance mechanism but even early after telomerase inactivation (Lundblad and Blackburn 1993;Le et al 1999;Khadaroo et al 2009;Churikov et al 2014;Fallet et al 2014;Xu et al 2015;Claussin and Chang 2016;Lue and Yu 2017), this result suggests that telomerase-negative cells frequently experience telomere-related damage, activate the DNA damage checkpoint and undergo repair events such as break-induced replication (BIR).…”

Section: Adaptation In Telomere-induced Replicative Senescencementioning

confidence: 99%

Adaptation in replicative senescence: a risky business

Coutelier

2019

Curr Genet

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Cell proliferation is tightly regulated to avoid propagating DNA damage and mutations, which can lead to pathologies such as cancer. To ensure genome integrity, cells activate the DNA damage checkpoint in response to genotoxic lesions to block cell cycle progression. This surveillance mechanism provides time to repair the damage before resuming cell cycle with an intact genome. When the damage is not repaired, cells can, in some conditions, override the cell cycle arrest and proceed with proliferation, a phenomenon known as adaptation to DNA damage. A subpopulation of adapted cells might eventually survive, but only at the cost of extensive genome instability. How and in which context adaptation operates the trade-off between survival and genome stability is a fascinating question. After a brief review of the current knowledge on adaptation to DNA damage in budding yeast, we will discuss a new role of adaptation in the context of telomerase-negative cells and replicative senescence. We highlight the idea that, in all settings studied so far, survival through adaptation is a double-edged sword as it comes with increased genomic instability.

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Telomere recombination pathways: tales of several unhappy marriages

Abstract: All happy families are alike; each unhappy family is unhappy in its own way. --Leo Tolstoy, Anna Karenina

Cited by 19 publications

References 71 publications

The role of genomic location and flanking 3′UTR in the generation of functional levels of variant surface glycoprotein in Trypanosoma brucei

The role of genomic location and flanking 3′UTR in the generation of functional levels of variant surface glycoprotein in Trypanosoma brucei

Keep moving and stay in a good shape to find your homologous recombination partner

Adaptation in replicative senescence: a risky business

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