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Telomere Length Homeostasis Responds to Changes in Intracellular dNTP Pools
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
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2013 (English)In: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 193, no 4, 1095-1105 p.Article in journal (Refereed) Published
Abstract [en]

Telomeres, the ends of linear eukaryotic chromosomes, shorten due to incomplete DNA replication and nucleolytic degradation. Cells counteract this shortening by employing a specialized reverse transcriptase called telomerase, which uses deoxyribonucleoside triphosphates (dNTPs) to extend telomeres. Intracellular dNTP levels are tightly regulated and perturbation of these levels is known to affect DNA synthesis. We examined whether altering the levels of the dNTP pools or changing the relative ratios of the four dNTPs in Saccharomyces cerevisiae would affect the length of the telomeres. Lowering dNTP levels leads to a modest shortening of telomeres, while increasing dNTP pools has no significant effect on telomere length. Strikingly, altering the ratio of the four dNTPs dramatically affects telomere length homeostasis, both positively and negatively. Specifically, we find that intracellular dGTP levels positively correlate with both telomere length and telomerase nucleotide addition processivity in vivo. Our findings are consistent with in vitro data showing dGTP-dependent stimulation of telomerase activity in multiple organisms, and suggest that telomerase activity is modulated in vivo by dGTP levels.

Place, publisher, year, edition, pages
The Genetics Society, 2013. Vol. 193, no 4, 1095-1105 p.
Keyword [en]
telomeres, telomere length homeostasis, dNTPs, telomerase, processivity
National Category
Cell and Molecular Biology
URN: urn:nbn:se:umu:diva-66608DOI: 10.1534/genetics.112.149120ISI: 000316937300006PubMedID: 23335335OAI: diva2:608067
Available from: 2013-02-26 Created: 2013-02-26 Last updated: 2014-12-05Bibliographically approved

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Sharma, SushmaMarjavaara, LisetteNilsson, Anna KarinChabes, Andrei
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Department of Medical Biochemistry and Biophysics
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