A sharp Pif1-dependent threshold separates DNA double-strand breaks from critically short telomeres

被引:20
|
作者
Strecker, Jonathan [1 ,2 ]
Stinus, Sonia [3 ]
Caballero, Mariana Pliego [3 ]
Szilard, Rachel K. [1 ]
Chang, Michael [3 ]
Durocher, Daniel [1 ,2 ]
机构
[1] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Room 1073 600 Univ Ave, Toronto, ON M5G 1X5, Canada
[2] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada
[3] Univ Groningen, Univ Med Ctr Groningen, European Res Inst Biol Ageing, A Deusinglaan 1, NL-9713 AV Groningen, Netherlands
来源
ELIFE | 2017年 / 6卷
关键词
SACCHAROMYCES-CEREVISIAE TELOMERES; REPEAT DIVERGENCE; LENGTH REGULATION; CHROMOSOME ENDS; PROTEIN CDC13; YEAST; BINDING; ELONGATION; SEQUENCES; DIMERIZATION;
D O I
10.7554/eLife.23783
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
DNA double-strand breaks (DSBs) and short telomeres are structurally similar, yet have diametrically opposed fates. Cells must repair DSBs while blocking the action of telomerase on these ends. Short telomeres must avoid recognition by the DNA damage response while promoting telomerase recruitment. In Saccharomyces cerevisiae, the Pif1 helicase, a telomerase inhibitor, lies at the interface of these end-fate decisions. Using Pif1 as a sensor, we uncover a transition point in which 34 bp of telomeric (TG(1-3))(n) repeat sequence renders a DNA end insensitive to Pif1 action, thereby enabling extension by telomerase. A similar transition point exists at natural chromosome ends, where telomeres shorter than similar to 40 bp are inefficiently extended by telomerase. This phenomenon is not due to known Pif1 modifications and we instead propose that Cdc13 renders TG(34+) ends insensitive to Pif1 action. We contend that the observed threshold of Pif1 activity defines a dividing line between DSBs and telomeres.
引用
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页数:59
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