Telomere Length Homeostasis Responds to Changes in Intracellular dNTP Pools

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.

Sharma, SushmaUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)sush0003 (author)
Reichenbach, Patrick (author)
Marjavaara, LisetteUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)lietoa93 (author)
Nilsson, Anna KarinUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)anni0002 (author)
Lingner, Joachim (author)
Chabes, AndreiUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)anch0002 (author)
Rothstein, Rodney (author)
Chang, Michael (author)
Umeå universitetInstitutionen för medicinsk kemi och biofysik (creator_code:org_t)

By the author/editor: Gupta, Amitabha; Sharma, Sushma; Reichenbach, Pat ...; Marjavaara, Lise ...; Nilsson, Anna Ka ...; Lingner, Joachim; show more...; Chabes, Andrei; Rothstein, Rodne ...; Chang, Michael; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.