title: Telomere length homeostasis responds to changes in intracellular dNTP pools.
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.
authors: Department of Cellular, Molecular and Biophysical Studies, Columbia University Medical Center, New York, NY 10032, USA.
authors: Amitabha
authors: A
authors: Gupta
authors: Sushma
authors: S
authors: Sharma
authors: Patrick
authors: P
authors: Reichenbach
authors: Lisette
authors: L
authors: Marjavaara
authors: Anna Karin
authors: AK
authors: Nilsson
authors: Joachim
authors: J
authors: Lingner
authors: Andrei
authors: A
authors: Chabes
authors: Rodney
authors: R
authors: Rothstein
authors: Michael
authors: M
authors: Chang
mesh_terms: D009711:Nucleotides / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000378:metabolism; D059505:Telomere Homeostasis; D059506:Telomere Shortening
chemical_list: D009711:Nucleotides; D029701:Saccharomyces cerevisiae Proteins; D019098:Telomerase