Telomeres are nucleoprotein complexes that protect the chromosome-ends from eliciting DNA repair while ensuring their complete duplication. Pot1 is a subunit of telomere capping complex that binds to the G-rich overhang and inhibits the activation of DNA damage checkpoints. In this study, we explore new functions of fission yeast Pot1 by using a pot1-1 temperature sensitive mutant. We show that pot1 inactivation impairs telomere DNA replication resulting in the accumulation of ssDNA leading to the complete loss of telomeric DNA. Recruitment of Stn1 to telomeres, an auxiliary factor of DNA lagging strand synthesis, is reduced in pot1-1 mutants and overexpression of Stn1 rescues loss of telomeres and cell viability at restrictive temperature. We propose that Pot1 plays a crucial function in telomere DNA replication by recruiting Stn1-Ten1 and Pol alpha-primase complex to telomeres via Tpz1, thus promoting lagging-strand DNA synthesis at stalled replication forks. [GRAPHICS] .
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Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USACase Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA
Xu, Mengyuan
Kiselar, Janna
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Case Western Reserve Univ, Ctr Prote & Bioinformat, Cleveland, OH 44106 USACase Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA
Kiselar, Janna
Whited, Tawna L.
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Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USACase Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA
Whited, Tawna L.
Hernandez-Sanchez, Wilnelly
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Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USACase Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA
Hernandez-Sanchez, Wilnelly
Taylor, Derek J.
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Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA
Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USACase Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA