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Genetics. 2013 Apr;193(4):1095-105. doi: 10.1534/genetics.112.149120. Epub 2013 Jan 18.

Telomere length homeostasis responds to changes in intracellular dNTP pools.

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1
Department of Cellular, Molecular and Biophysical Studies, Columbia University Medical Center, New York, NY 10032, USA.

Abstract

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 deoxyguanosine triphosphate (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.

PMID:
23335335
PMCID:
PMC3606089
DOI:
10.1534/genetics.112.149120
[Indexed for MEDLINE]
Free PMC Article
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