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Persistent telomere cohesion protects aged cells from premature senescence

View ORCID ProfileKameron Azarm, Amit Bhardwaj, Eugenie Kim, View ORCID ProfileSusan Smith
doi: https://doi.org/10.1101/2020.02.03.932145
Kameron Azarm
Kimmel Center for Biology and Medicine at the Skirball Institute Department of Pathology New York University School of Medicine New York, NY 10016
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Amit Bhardwaj
Kimmel Center for Biology and Medicine at the Skirball Institute Department of Pathology New York University School of Medicine New York, NY 10016
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Eugenie Kim
Kimmel Center for Biology and Medicine at the Skirball Institute Department of Pathology New York University School of Medicine New York, NY 10016
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Susan Smith
Kimmel Center for Biology and Medicine at the Skirball Institute Department of Pathology New York University School of Medicine New York, NY 10016
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  • For correspondence: susan.smith@med.nyu.edu
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Abstract

Human telomeres are bound by the telomere repeat binding proteins TRF1 and TRF2. Telomere shortening in human cells leads to a DNA damage response that signals replicative senescence. While insufficient loading of TRF2 at shortened telomeres contributes to the DNA damage response in senescence, the contribution of TRF1 to senescence induction has not been determined. Here we show that counter to TRF2 deficiency-mediated induction of DNA damage, TRF1 deficiency serves a protective role to limit induction of DNA damage induced by subtelomere recombination. Shortened telomeres recruit insufficient TRF1 and as a consequence inadequate tankyrase 1 to resolve sister telomere cohesion. The persistent cohesion protects short telomeres from inappropriate recombination. Ultimately, in the final division, telomeres are no longer able to maintain cohesion and subtelomere copying ensues. Thus, the gradual loss of TRF1 and concomitant persistent cohesion that occurs with telomere shortening ensures a measured approach to replicative senescence.

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Posted February 03, 2020.
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Persistent telomere cohesion protects aged cells from premature senescence
Kameron Azarm, Amit Bhardwaj, Eugenie Kim, Susan Smith
bioRxiv 2020.02.03.932145; doi: https://doi.org/10.1101/2020.02.03.932145
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Persistent telomere cohesion protects aged cells from premature senescence
Kameron Azarm, Amit Bhardwaj, Eugenie Kim, Susan Smith
bioRxiv 2020.02.03.932145; doi: https://doi.org/10.1101/2020.02.03.932145

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