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Telomere Length Homeostasis Responds to Changes in Intracellular dNTP Pools
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
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2013 (engelsk)Inngår i: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 193, nr 4, s. 1095-1105Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
The Genetics Society, 2013. Vol. 193, nr 4, s. 1095-1105
Emneord [en]
telomeres, telomere length homeostasis, dNTPs, telomerase, processivity
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Identifikatorer
URN: urn:nbn:se:umu:diva-66608DOI: 10.1534/genetics.112.149120ISI: 000316937300006PubMedID: 23335335OAI: oai:DiVA.org:umu-66608DiVA, id: diva2:608067
Tilgjengelig fra: 2013-02-26 Laget: 2013-02-26 Sist oppdatert: 2018-06-08bibliografisk kontrollert

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